Skip to main content
Log in

Pharmacological Effects of Formulation Vehicles

Implications for Cancer Chemotherapy

  • Review Article
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Abstract

The non-ionic surfactants Cremophor® EL (CrEL; polyoxyethyleneglycerol triricinoleate 35) and polysorbate 80 (Tween® 80; polyoxy-ethylene-sorbitan-20-monooleate) are widely used as drug formulation vehicles, including for the taxane anticancer agents paclitaxel and docetaxel. A wealth of recent experimental data has indicated that both solubilisers are biologically and pharmacologically active compounds, and their use as drug formulation vehicles has been implicated in clinically important adverse effects, including acute hypersensitivity reactions and peripheral neuropathy.

CrEL and Tween® 80 have also been demonstrated to influence the disposition of solubilised drugs that are administered intravenously. The overall resulting effect is a highly increased systemic drug exposure and a simultaneously decreased clearance, leading to alteration in the pharmacodynamic characteristics of the solubilised drug. Kinetic experiments revealed that this effect is primarily caused by reduced cellular uptake of the drug from large spherical micellar-like structures with a highly hydrophobic interior, which act as the principal carrier of circulating drug. Within the central blood compartment, this results in a profound alteration of drug accumulation in erythrocytes, thereby reducing the free drug fraction available for cellular partitioning and influencing drug distribution as well as elimination routes. The existence of CrEL and Tween® 80 in blood as large polar micelles has also raised additional complexities in the case of combination chemotherapy regimens with taxanes, such that the disposition of several coadministered drugs, including anthracyclines and epipodophyllotoxins, is significantly altered. In contrast to the enhancing effects of Tween® 80, addition of CrEL to the formulation of oral drug preparations seems to result in significantly diminished drug uptake and reduced circulating concentrations.

The drawbacks presented by the presence of CrEL or Tween® 80 in drug formulations have instigated extensive research to develop alternative delivery forms. Currently, several strategies are in progress to develop Tween® 80- and CrEL-free formulations of docetaxel and paclitaxel, which are based on pharmaceutical (e.g. albumin nanoparticles, emulsions and liposomes), chemical (e.g. polyglutamates, analogues and prodrugs), or biological (e.g. oral drug administration) strategies. These continued investigations should eventually lead to more rational and selective chemotherapeutic treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1
Fig. 2
Table II
Fig. 3
Table III
Fig. 4
Table IV
Fig. 5
Table V
Fig. 6
Table VI
Fig. 7
Table VII
Fig. 8
Table VIII
Table IX

Similar content being viewed by others

Notes

  1. Use of tradenames is for product identification only and does not imply endorsement.

References

  1. Wani MC, Taylor HL, Wall ME, et al. Plant antitumor agents: VI. the isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 1971; 93: 2325–7

    Article  PubMed  CAS  Google Scholar 

  2. Adams JD, Flora KP, Goldspiel BR, et al. Taxol: a history of pharmaceutical development and current pharmaceutical concerns. J Natl Cancer Inst Monogr 1993; 15: 141–7

    PubMed  Google Scholar 

  3. Dorr RT. Pharmacology and toxicology of Cremophor EL diluent. Ann Pharmacother 1994; 28 Suppl. 5: S11–4

    PubMed  CAS  Google Scholar 

  4. Bissery MC. Preclinical pharmacology of docetaxel. Eur J Cancer 1995; 31A Suppl. 4: S1–6

    Article  PubMed  CAS  Google Scholar 

  5. Meyer T, Waidelich D, Frahm AW. Separation and first structure elucidation of Cremophor® EL components by hyphenated capillary electrophoresis and delayed extraction-matrix assisted laser desorption/ionization-time of flight mass spectrometry. Electrophoresis 2002; 23: 1053–62

    Article  PubMed  CAS  Google Scholar 

  6. Boyle DA, Goldspiel BR. A review of paclitaxel (Taxol) administration, stability, and compatibility issues. Clin J Oncol Nurs 1998; 2: 141–5

    PubMed  CAS  Google Scholar 

  7. Waugh WN, Trissel LA, Stella VJ. Stability, compatibility, and plasticizer extraction of taxol (NSC-125973) injection diluted in infusion solutions and stored in various containers. Am J Hosp Pharm 1991; 48: 1520–4

    PubMed  CAS  Google Scholar 

  8. Sparreboom A, van Zuylen L, Brouwer E, et al. Cremophor EL-mediated alteration of paclitaxel distribution in human blood: clinical pharmacokinetic implications. Cancer Res 1999; 59: 1454–7

    PubMed  CAS  Google Scholar 

  9. Weiss RB, Donehower RC, Wiernik PH, et al. Hypersensitivity reactions from taxol. J Clin Oncol 1990; 8: 1263–8

    PubMed  CAS  Google Scholar 

  10. Hayes FA, Abromowitch M, Green AA. Allergic reactions to teniposide in patients with neuroblastoma and lymphoid malignancies. Cancer Treat Rep 1985; 69: 439–41

    PubMed  CAS  Google Scholar 

  11. Dye D, Watkins J. Suspected anaphylactic reaction to Cremophor EL. BMJ 1980; 280: 1353

    Article  PubMed  CAS  Google Scholar 

  12. Volcheck GW, Van Dellen RG. Anaphylaxie to intravenous cyclosporine and tolerance to oral cyclosporine: case report and review. Ann Allergy Asthma Immunol 1998; 80: 159–63

    Article  PubMed  CAS  Google Scholar 

  13. Essayan DM, Kagey-Sobotka A, Colarusso PJ, et al. Successful parenteral desensitization to paclitaxel. J Allergy Clin Immunol 1996; 97: 42–6

    Article  PubMed  CAS  Google Scholar 

  14. Huttel MS, Schou OA, Stoffersen E. Complement-mediated reactions to diazepam with Cremophor as solvent (Stesolid MR). Br J Anaesth 1980; 52: 77–9

    Article  PubMed  CAS  Google Scholar 

  15. Strachan EB. Case report: suspected anaphylactic reaction to Cremophor EL. SAAD Dig 1981; 4: 209

    PubMed  CAS  Google Scholar 

  16. Szebeni J, Muggia FM, Alving CR. Complement activation by Cremophor EL as a possible contributor to hypersensitivity to paclitaxel: an in vitro study. J Natl Cancer Inst 1998; 90: 300–6

    Article  PubMed  CAS  Google Scholar 

  17. van Zuylen L, Gianni L, Verweij J, et al. Inter-relationships of paclitaxel disposition, infusion duration and Cremophor EL kinetics in cancer patients. Anticancer Drugs 2000; 11: 331–7

    Article  PubMed  Google Scholar 

  18. Theis JG, Liau-Chu M, Chan HS, et al. Anaphylactoid reactions in children receiving high-dose intravenous cyclosporine for reversal of tumor resistance: the causative role of improper dissolution of Cremophor EL. J Clin Oncol 1995; 13: 2508–16

    PubMed  CAS  Google Scholar 

  19. Loos WJ, Szebeni J, ten Tije AJ, et al. Preclinical evaluation of alternative pharmaceutical delivery vehicles for paclitaxel. Anticancer Drugs 2002; 13: 767–75

    Article  PubMed  CAS  Google Scholar 

  20. Lorenz W, Schmal A, Schult H, et al. Histamine release and hypotensive reactions in dogs by solubilizing agents and fatty acids: analysis of various components in Cremophor EL and development of a compound with reduced toxicity. Agents Actions 1982; 12: 64–80

    Article  PubMed  CAS  Google Scholar 

  21. Michaud LB. Methods for preventing reactions secondary to Cremophor EL. Ann Pharmacother 1997; 31: 1402–4

    PubMed  CAS  Google Scholar 

  22. Price KS, Castells MC. Taxol reactions. Allergy Asthma Proc 2002; 23: 205–8

    PubMed  Google Scholar 

  23. Rowinsky EK, Eisenhauer EA, Chaudhry V, et al. Clinical toxicities encountered with paclitaxel (Taxol). Semin Oncol 1993; 20 Suppl. 3: 1–15

    PubMed  CAS  Google Scholar 

  24. Rowinsky EK, Burke PJ, Karp JE, et al. Phase I and pharmacodynamic study of taxol in refractory acute leukemias. Cancer Res 1989; 49: 4640–7

    PubMed  CAS  Google Scholar 

  25. Siderov J, Prasad P, De Boer R, et al. Safe administration of etoposide phosphate after hypersensitivity reaction to intravenous etoposide. Br J Cancer 2002; 86: 12–3

    Article  PubMed  CAS  Google Scholar 

  26. Os’Dwyer PJ, Weiss RB. Hypersensitivity reactions induced by etoposide. Cancer Treat Rep 1984; 68: 959–61

    Google Scholar 

  27. Hoetelmans RM, Schornagel JH, ten Bokkel Huinink WW, et al. Hypersensitivity reactions to etoposide. Ann Pharmacother 1996; 30: 367–71

    PubMed  CAS  Google Scholar 

  28. Bernstein BJ, Troner MB. Successful rechallenge with etoposide phosphate after an acute hypersensitivity reaction to etoposide. Pharmacotherapy 1999; 19: 989–91

    Article  PubMed  CAS  Google Scholar 

  29. Burris H, Irvin R, Kuhn J, et al. Phase I clinical trial of Taxotere administered as either a 2-hour or 6- hour intravenous infusion. J Clin Oncol 1993; 11: 950–8

    PubMed  CAS  Google Scholar 

  30. Piccart MJ, Gore M, ten Bokkel Huinink WW, et al. Docetaxel: an active new drug for treatment of advanced epithelial ovarian cancer. J Natl Cancer Inst 1995; 87: 676–81

    Article  PubMed  CAS  Google Scholar 

  31. Trudeau ME, Eisenhauer EA, Higgins BP, et al. Docetaxel in patients with metastatic breast cancer: a phase II study of the National Cancer Institute of Canada-Clinical Trials Group. J Clin Oncol 1996; 14: 422–8

    PubMed  CAS  Google Scholar 

  32. Eisenhauer EA, Trudeau M. An overview of phase II studies of docetaxel in patients with metastatic breast cancer. Eur J Cancer 1995; 31A Suppl. 4: S11–3

    Article  PubMed  CAS  Google Scholar 

  33. Bristol-Myers Squibb Inc. Taxol® (paclitaxel): prescribing information. Princeton, NJ: Bristol-Myers Squibb, 2003. Available online from: http://www.taxol.com/txpi.html [accessed 2003 May 13]

    Google Scholar 

  34. Aventis Pharmaceuticals Inc. Taxotere® (docetaxel): prescribing information. Bridgewater, NJ: Aventis Pharmaceuticals, 2002. Available online from: http://www.taxotere.com/resources/piframes.html [accessed 2003 May 13]

    Google Scholar 

  35. Wiernik PH, Schwartz EL, Strauman JJ, et al. Phase I clinical and pharmacokinetic study of taxol. Cancer Res 1987; 47: 2486–93

    PubMed  CAS  Google Scholar 

  36. Lesser GJ, Grossman SA, Eller S, et al. The distribution of systemically administered [3H]-paclitaxel in rats: a quantitative autoradiographic study. Cancer Chemother Pharmacol 1995; 37: 173–8

    PubMed  CAS  Google Scholar 

  37. Onetto N, Canetta R, Winograd B, et al. Overview of taxol safety. J Natl Cancer Inst Monogr 1993; 15: 131–9

    PubMed  Google Scholar 

  38. de Groen PC, Aksamit AJ, Rakela J, et al. Central nervous system toxicity after liver transplantation: the role of cyclosporine and cholesterol. N Engl J Med 1987; 317: 861–6

    Article  PubMed  Google Scholar 

  39. Windebank AJ, Blexrud MD, de Groen PC. Potential neurotoxicity of the solvent vehicle for cyclosporine. J Pharmacol Exp Ther 1994; 268: 1051–6

    PubMed  CAS  Google Scholar 

  40. Boer HH, Moorer-van Delft CM, Muller LJ, et al. Ultrastructural neuropathologic effects of Taxol on neurons of the freshwater snail Lymnaea stagnalis. J Neurooncol 1995; 25: 49–57

    Article  PubMed  CAS  Google Scholar 

  41. Brat DJ, Windebank AJ, Brimijoin S. Emulsifier for intravenous cyclosporin inhibits neurite outgrowth, causes deficits in rapid axonal transport and leads to structural abnormalities in differentiating N1E.115 neuroblastoma. J Pharmacol Exp Ther 1992; 261: 803–10

    PubMed  CAS  Google Scholar 

  42. New PZ, Jackson CE, Rinaldi D, et al. Peripheral neuropathy secondary to docetaxel (Taxotere). Neurology 1996; 46: 108–11

    Article  PubMed  CAS  Google Scholar 

  43. Hilkens PH, Verweij J, Vecht CJ, et al. Clinical characteristics of severe peripheral neuropathy induced by docetaxel (Taxotere). Ann Oncol 1997; 8: 187–90

    Article  PubMed  CAS  Google Scholar 

  44. Hilkens PH, Verweij J, Stoter G, et al. Peripheral neurotoxicity induced by docetaxel. Neurology 1996; 46: 104–8

    Article  PubMed  CAS  Google Scholar 

  45. Pronk LC, Hilkens PH, van den Bent MJ, et al. Corticosteroid co-medication does not reduce the incidence and severity of neurotoxicity induced by docetaxel. Anticancer Drugs 1998; 9: 759–64

    Article  PubMed  CAS  Google Scholar 

  46. Verweij J, Clavel M, Chevalier B. Paclitaxel (Taxol) and docetaxel (Taxotere): not simply two of a kind. Ann Oncol 1994; 5: 495–505

    PubMed  CAS  Google Scholar 

  47. Freilich RJ, Balmaceda C, Scidman AD, et al. Motor neuropathy due to docetaxel and paclitaxel. Neurology 1996; 47: 115–8

    Article  PubMed  CAS  Google Scholar 

  48. Bagnarello AG, Lewis LA, McHenry MC, et al. Unusual serum lipoprotein abnormality induced by the vehicle of miconazole. N Engl J Med 1977; 296: 497–9

    Article  PubMed  CAS  Google Scholar 

  49. Kongshaug M, Cheng LS, Moan J, et al. Interaction of Cremophor EL with human plasma. Int J Biochem 1991; 23: 473–8

    Article  PubMed  CAS  Google Scholar 

  50. Woodburn K, Kessel D. The alteration of plasma lipoproteins by Cremophor EL. J Photochem Photobiol B 1994; 22: 197–201

    Article  PubMed  CAS  Google Scholar 

  51. Kessel D, Woodburn K, Decker D, et al. Fractionation of Cremophor EL delineates components responsible for plasma lipoprotein alterations and multidrug resistance reversal. Oncol Res 1995; 7: 207–12

    PubMed  CAS  Google Scholar 

  52. Sykes E, Woodburn K, Decker D, et al. Effects of Cremophor EL on distribution of Taxol to serum lipoproteins. Br J Cancer 1994; 70: 401–4

    Article  PubMed  CAS  Google Scholar 

  53. Shimomura T, Fujiwara H, Ikawa S, et al. Effects of Taxol on blood cells. Lancet 1998; 352: 541–2

    Article  PubMed  CAS  Google Scholar 

  54. Ferns G, Reidy M, Ross R. Vascular effects of cyclosporine A in vivo and in vitro. Am J Pathol 1990; 137: 403–13

    PubMed  CAS  Google Scholar 

  55. Tatou E, Mossiat C, Maupoil V, et al. Effects of cyclosporin and Cremophor on working rat heart and incidence of myocardial lipid peroxidation. Pharmacology 1996; 52: 1–7

    Article  PubMed  CAS  Google Scholar 

  56. Kartner N, Riordan JR, Ling V. Cell surface P-glycoprotein associated with multidrug resistance in mammalian cell lines. Science 1983; 221: 1285–8

    Article  PubMed  CAS  Google Scholar 

  57. Kartner N, Evernden-Porelle D, Bradley G, et al. Detection of P-glycoprotein in multidrug-resistant cell lines by monoclonal antibodies. Nature 1985; 316: 820–3

    Article  PubMed  CAS  Google Scholar 

  58. Woodcock DM, Jefferson S, Linsenmeyer ME, et al. Reversal of the multidrug resistance phenotype with Cremophor EL, a common vehicle for water-insoluble vitamins and drugs. Cancer Res 1990; 50: 4199–203

    PubMed  CAS  Google Scholar 

  59. Schuurhuis GJ, Broxterman HJ, Pinedo HM, et al. The polyoxyethylene castor oil Cremophor EL modifies multidrug resistance. Br J Cancer 1990; 62: 591–4

    Article  PubMed  CAS  Google Scholar 

  60. Chervinsky DS, Brecher ML, Hoelcle MJ. Cremophor-EL enhances taxol efficacy in a multi-drug resistant C1300 neuroblastoma cell line. Anticancer Res 1993; 13: 93–6

    PubMed  CAS  Google Scholar 

  61. Riehm H, Biedler JL. Potentiation of drug effect by Tween 80 in Chinese hamster cells resistant to actinomycin D and daunomycin. Cancer Res 1972; 32: 1195–200

    PubMed  CAS  Google Scholar 

  62. Friche E, Jensen PB, Sehested M, et al. The solvents Cremophor EL and Tween 80 modulate daunorubicin resistance in the multidrug resistant Ehrlich ascites tumor. Cancer Commun 1990; 2: 297–303

    PubMed  CAS  Google Scholar 

  63. Coon JS, Knudson W, Clodfelter K, et al. Solutol HS 15, nontoxic polyoxyethylene esters of 12-hydroxystearic acid, reverses multidrug resistance. Cancer Res 1991; 51: 897–902

    PubMed  CAS  Google Scholar 

  64. Zordan-Nudo T, Ling V, Liu Z, et al. Effects of nonionic detergents on P-glycoprotein drug binding and reversal of multidrug resistance. Cancer Res 1993; 53: 5994–6000

    PubMed  CAS  Google Scholar 

  65. Woodcock DM, Linsenmeyer ME, Chojnowski G, et al. Reversal of multidrug resistance by surfactants. Br J Cancer 1992; 66: 62–8

    Article  PubMed  CAS  Google Scholar 

  66. Slater L, Sweet P, Wetzel M, et al. Comparison of cyclosporin A, Verapamil, PSC-833 and Cremophor EL as enhancing agents of VP-16 in murine lymphoid leukemias. Leuk Res 1995; 19: 543–8

    Article  PubMed  CAS  Google Scholar 

  67. Watanabe T, Nakayama Y, Naito M, et al. Cremophor EL reversed multidrug resistance in vitro but not in tumor- bearing mouse models. Anticancer Drugs 1996; 7: 825–32

    Article  PubMed  CAS  Google Scholar 

  68. Sparreboom A, Verweij J, van der Burg ME, et al. Disposition of Cremophor EL in humans limits the potential for modulation of the multidrug resistance phenotype in vivo. Clin Cancer Res 1998; 4: 1937–42

    PubMed  CAS  Google Scholar 

  69. Nooter K, Sonneveld P. Clinical relevance of P-glycoprotein expression in haematological malignancies. Leuk Res 1994; 18: 233–43

    Article  PubMed  CAS  Google Scholar 

  70. Fjallskog ML, Frii L, Bergh J. Is Cremophor EL, solvent for paclitaxel, cytotoxic [letter]. Lancet 1993; 342: 873

    Article  PubMed  CAS  Google Scholar 

  71. Fjallskog ML, Frii L, Bergh J. Paclitaxel-induced cytotoxicity: the effects of Cremophor EL (castor oil) on two human breast cancer cell lines with acquired multidrug resistant phenotype and induced expression of the permeability glycoprotein. Eur J Cancer 1994; 30A: 687–90

    Article  PubMed  CAS  Google Scholar 

  72. Nygren P, Csoka K, Jonsson B, et al. The cytotoxic activity of Taxol in primary cultures of tumour cells from patients is partly mediated by Cremophor EL. Br J Cancer 1995; 71: 478–81

    Article  PubMed  CAS  Google Scholar 

  73. Csoka K, Dhar S, Fridborg H, et al. Differential activity of Cremophor EL and paclitaxel in patientss’ tumor cells and human carcinoma cell lines in vitro. Cancer 1997; 79: 1225–33

    Article  PubMed  CAS  Google Scholar 

  74. Begin ME, Ells G, Horrobin DF. Polyunsaturated fatty acidinduced cytotoxicity against tumor cells and its relationship to lipid peroxidation. J Natl Cancer Inst 1988; 80: 188–94

    Article  PubMed  CAS  Google Scholar 

  75. Siegel I, Liu TL, Yaghoubzadeh E, et al. Cytotoxic effects of free fatty acids on ascites tumor cells. J Natl Cancer Inst 1987; 78: 271–7

    PubMed  CAS  Google Scholar 

  76. Burton AF. Oncolytic effects of fatty acids in mice and rats. Am J Clin Nutr 1991; 53 Suppl. 4: 1082S–6S

    PubMed  CAS  Google Scholar 

  77. Liebmann J, Cook JA, Lipschultz C, et al. The influence of Cremophor EL on the cell cycle effects of paclitaxel (Taxol) in human tumor cell lines. Cancer Chemother Pharmacol 1994; 33: 331–9

    Article  PubMed  CAS  Google Scholar 

  78. Kay ER. Effects of Tween 80 on the growth of the Ehrlich-Lettre ascites carcinoma. Experientia 1965; 21: 644–5

    Article  PubMed  CAS  Google Scholar 

  79. Kubis A, Witek R, Olszewski Z, et al. The cytotoxic effect of Tween 80 on Ehrlich ascites cancer cells in mice. Pharmazie 1979; 34: 745–6

    PubMed  CAS  Google Scholar 

  80. Witek R, Krupa S, Kubis A. Cytotoxic action of diethanolamine oleate on Ehrlich exudative carcinoma in mice, compared with the action of polyoxyethylene sorbitan mono-oleate (Tween 80). Arch Immunol Ther Exp (Warsz) 1979; 27: 321–4

    CAS  Google Scholar 

  81. Chajes V, Sattler W, Stranzl A, et al. Influence of n-3 fatty acids on the growth of human breast cancer cells in vitro: relationship to peroxides and vitamin-E. Breast Cancer Res Treat 1995; 34: 199–212

    Article  PubMed  CAS  Google Scholar 

  82. Kimura Y. Carp oil or oleic acid, but not linoleic acid or linolenic acid, inhibits tumor growth and metastasis in Lewis lung carcinoma-bearing mice. J Nutr 2002; 132: 2069–75

    PubMed  CAS  Google Scholar 

  83. Webster L, Linsenmeyer M, Millward M, et al. Measurement of Cremophor EL following taxol: plasma levels sufficient to reverse drug exclusion mediated by the multidrug-resistant phenotype. J Natl Cancer Inst 1993; 85: 1685–90

    Article  PubMed  CAS  Google Scholar 

  84. Sparreboom A, Van Tellingen O, Huizing MT, et al. Determination of polyoxyethylene glycerol triricinoleate 35 (Cremophor EL) in plasma by pre-column derivatization and reversed-phase high-performance liquid chromatography. J Chromatogr B Biomed Appl 1996; 681: 355–62

    Article  PubMed  CAS  Google Scholar 

  85. Sparreboom A, Loos WJ, Verweij J, et al. Quantitation of Cremophor EL in human plasma samples using a colorimetric dye-binding microassay. Anal Biochem 1998; 255: 171–5

    Article  PubMed  CAS  Google Scholar 

  86. Brouwer E, Verweij J, Hauns B, et al. Linearized colorimetric assay for Cremophor EL: application to pharmacokinetics after 1-hour paclitaxel infusions. Anal Biochem 1998; 261: 198–202

    Article  PubMed  CAS  Google Scholar 

  87. van Tellingen O, Beijnen JH, Verweij J, et al. Rapid esterasesensitive breakdown of polysorbate 80 and its impact on the plasma pharmacokinetics of docetaxel and metabolites in mice. Clin Cancer Res 1999; 5: 2918–24

    PubMed  Google Scholar 

  88. Kunkel M, Meyer T, Bohler J, et al. Titrimetric determination of Cremophor EL in aqueous solutions and biofluids: part 2: ruggedness of the method with respect to biofluids. J Pharm Biomed Anal 1999; 21: 911–22

    Article  PubMed  CAS  Google Scholar 

  89. Smullin CF. Quantitative determination of polysorbate in non-standard salad dressings. J Assoc Off Anal Chem 1978; 61: 506–7

    PubMed  CAS  Google Scholar 

  90. Smullin CF, Wetterau FP, Olsanski VL. The determination of polysorbate 60 in foods. J Am Oil Chem Soc 1971; 48: 18–20

    Article  PubMed  CAS  Google Scholar 

  91. McKean DL, Pesce AJ, Koo W. Analysis of polysorbate and its polyoxyethylated metabolite. Anal Biochem 1987; 161: 348–51

    Article  PubMed  CAS  Google Scholar 

  92. Kato H, Nagai Y, Yamamoto K, et al. Determination of polysorbates in foods by colorimetry with confirmation by infrared spectrophotometry, thin-layer chromatography, and gas chromatography. J Assoc Off Anal Chem 1989; 72: 27–9

    PubMed  CAS  Google Scholar 

  93. McKean DL, Pesce AJ. Determination of polysorbate in ascites fluid from a premature infant. J Anal Toxicol 1985; 9: 174–6

    PubMed  CAS  Google Scholar 

  94. Takeda Y, Abe Y, Ishiwata H, et al. [Determination method of polysorbates in powdered soup by HPLC]. Shokuhin Eiseigaku Zasshi 2001; 42: 91–5

    Article  PubMed  CAS  Google Scholar 

  95. Oszi Z, Petho G. Quantitative determination of polysorbate 20 in nasal pharmaceutical preparations by high-performance liquid chromatography. J Pharm Biomed Anal 1998; 18: 715–20

    Article  PubMed  CAS  Google Scholar 

  96. Sparreboom A, Zhao M, Brahmer JR, et al. Determination of the docetaxel vehicle, polysorbate 80, in patient samples by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2002; 773: 183–90

    Article  PubMed  CAS  Google Scholar 

  97. Meerum-Terwogt JM, van Tellingen O, Nannan P, et al. Cremophor EL pharmacokinetics in a phase I study of paclitaxel (Taxol) and carboplatin in non-small cell lung cancer patients. Anticancer Drugs 2000; 11: 687–94

    Article  PubMed  CAS  Google Scholar 

  98. van den Bongard HJ, Mathot RA, van Tellingen O, et al. A population pharmacokinetic model for Cremophor EL using nonlinear mixed-effect modeling: model building and validation [abstract]. Br J Clin Pharmacol 2002; 53: 552P–3P

    Article  Google Scholar 

  99. van den Bongard HJ, Mathot RA, van Tellingen O, et al. A population analysis of the pharmacokinetics of Cremophor EL using nonlinear mixed-effect modelling. Cancer Chemother Pharmacol 2002; 50: 16–24

    Article  PubMed  CAS  Google Scholar 

  100. Eisenhauer EA, ten Bokkel Huinink WW, Swenerton KD, et al. European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion. J Clin Oncol 1994; 12: 2654–66

    PubMed  CAS  Google Scholar 

  101. Mielke S, Mross K, Glocker F, et al. Neurotoxicity of paclitaxel infused weekly over one versus three hours [abstract]. Proc Am Soc Clin Oncol 2001; 20: 425

    Google Scholar 

  102. Gelderblom H, Mross K, ten Tije AJ, et al. Comparative pharmacokinetics of unbound paclitaxel during 1- and 3-hour infusions. J Clin Oncol 2002; 20: 574–81

    Article  PubMed  CAS  Google Scholar 

  103. Rischin D, Webster LK, Millward MJ, et al. Cremophor pharmacokinetics in patients receiving 3-, 6-, and 24-hour infusions of paclitaxel. J Natl Cancer Inst 1996; 88: 1297–301

    Article  PubMed  CAS  Google Scholar 

  104. Briasoulis E, Karavasilis V, Tzamakou E, et al. Pharmacodynamics of non-break weekly paclitaxel (Taxol) and pharmacokinetics of Cremophor-EL vehicle: results of a doseescalation study. Anticancer Drugs 2002; 13: 481–9

    Article  PubMed  CAS  Google Scholar 

  105. Panday VR, Huizing MT, Willemse PH, et al. Hepatic metabolism of paclitaxel and its impact in patients with altered hepatic function. Semin Oncol 1997; 24 Suppl. 11: S11–S8

    PubMed  CAS  Google Scholar 

  106. Gelderblom H, Verweij J, Brouwer E, et al. Disposition of [G-3H]paclitaxel and Cremophor EL in a patient with severely impaired renal function. Drug Metab Dispos 1999; 27: 1300–5

    PubMed  CAS  Google Scholar 

  107. Webster LK, Linsenmeyer ME, Rischin D, et al. Plasma concentrations of polysorbate 80 measured in patients following administration of docetaxel or etoposide. Cancer Chemother Pharmacol 1997; 39: 557–60

    Article  PubMed  CAS  Google Scholar 

  108. van Zuylen L, Verweij J, Sparreboom A. Role of formulation vehicles in taxane pharmacology. Invest New Drugs 2001; 19: 125–41

    Article  PubMed  Google Scholar 

  109. Ellis AG, Webster LK. Inhibition of paclitaxel elimination in the isolated perfused rat liver by Cremophor EL. Cancer Chemother Pharmacol 1999; 43: 13–8

    Article  PubMed  CAS  Google Scholar 

  110. Gianni L, Vigano L, Locatelli A, et al. Human pharmacokinetic characterization and in vitro study of the interaction between doxorubicin and paclitaxel in patients with breast cancer. J Clin Oncol 1997; 15: 1906–15

    PubMed  CAS  Google Scholar 

  111. Ellis AG, Crinis NA, Webster LK. Inhibition of etoposide elimination in the isolated perfused rat liver by Cremophor EL and Tween 80. Cancer Chemother Pharmacol 1996; 38: 81–7

    Article  PubMed  CAS  Google Scholar 

  112. Sparreboom A, van Asperen J, Mayer U, et al. Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc Natl Acad Sci U S A 1997; 94: 2031–5

    Article  PubMed  CAS  Google Scholar 

  113. Kurlansky PA, Sadeghi AM, Michler RE, et al. Role of the carrier solution in cyclosporine pharmacokinetics in the baboon. J Heart Transplant 1986; 5: 312–6

    PubMed  CAS  Google Scholar 

  114. Webster LK, Cosson EJ, Stokes KH, et al. Effect of the paclitaxel vehicle, Cremophor EL, on the pharmacokinetics of doxorubicin and doxorubicinol in mice. Br J Cancer 1996; 73: 522–4

    Article  PubMed  CAS  Google Scholar 

  115. Badary OA, Al Shabanah OA, Al Gharably NM, et al. Effect of Cremophor EL on the pharmacokinetics, antitumor activity and toxicity of doxorubicin in mice. Anticancer Drugs 1998; 9: 809–15

    Article  PubMed  CAS  Google Scholar 

  116. Colombo T, Parisi I, Zucchetti M, et al. Pharmacokinetic interactions of paclitaxel, docetaxel and their vehicles with doxorubicin. Ann Oncol 1999; 10: 391–5

    Article  PubMed  CAS  Google Scholar 

  117. Millward MJ, Webster LK, Rischin D, et al. Phase I trial of Cremophor EL with bolus doxorubicin. Clin Cancer Res 1998; 4: 2321–9

    PubMed  CAS  Google Scholar 

  118. Colombo T, Gonzalez PO, Zucchetti M, et al. Paclitaxel induces significant changes in epidoxorubicin distribution in mice. Ann Oncol 1996; 7: 801–5

    Article  PubMed  CAS  Google Scholar 

  119. Yamamoto N, Negoro S, Chikazawa H, et al. Pharmacokinetic interaction of the combination of paclitaxel and irinotecan in vivo and clinical study [abstract]. Proc Am Soc Clin Oncol 1999; 18: 187

    Google Scholar 

  120. Woodburn K, Chang CK, Lee S, et al. Biodistribution and PDT efficacy of a ketochlorin photosensitizer as a function of the delivery vehicle. Photochem Photobiol 1994; 60: 154–9

    Article  PubMed  CAS  Google Scholar 

  121. Liu J, Kraut EH, Balcerzak S, et al. Dosing sequence-dependent pharmacokinetic interaction of oxaliplatin with paclitaxel in the rat. Cancer Chemother Pharmacol 2002; 50: 445–53

    Article  PubMed  CAS  Google Scholar 

  122. Sparreboom A, van Tellingen O, Nooijen WJ, et al. Nonlinear pharmacokinetics of paclitaxel in mice results from the pharmaceutical vehicle Cremophor EL. Cancer Res 1996; 56: 2112–5

    PubMed  CAS  Google Scholar 

  123. Gelderblom H, Verweij J, van Zomeren DM, et al. Influence of Cremophor EL on the bioavailability of intraperitoneal paclitaxel. Clin Cancer Res 2002; 8: 1237–41

    PubMed  CAS  Google Scholar 

  124. Casazza AM, Pratesi G, Giuliani F, et al. Enhancement of the antitumor activity of adriamycin by Tween 80. Tumori 1978; 64: 115–29

    PubMed  CAS  Google Scholar 

  125. Harrison Jr SD, Cusic AM, McAfee SM. Tween 80 increases plasma adriamycin concentrations in mice by an apparent reduction of plasma volume. Eur J Cancer 1981; 17: 387–9

    PubMed  CAS  Google Scholar 

  126. Cummings J, Forrest GJ, Cunningham D, et al. Influence of polysorbate 80 (Tween 80) and etoposide (VP-16-213) on the pharmacokinetics and urinary excretion of adriamycin and its metabolites in cancer patients. Cancer Chemother Pharmacol 1986; 17: 80–4

    Article  PubMed  CAS  Google Scholar 

  127. Azmin MN, Stuart JF, Caiman KC, et al. Effects of polysorbate 80 on the absorption and distribution of oral methotrexate (MTX) in mice. Cancer Chemother Pharmacol 1982; 9: 161–4

    Article  PubMed  CAS  Google Scholar 

  128. Dimitrijevic D, Whitton PS, Domin M, et al. Increased vigabatrin entry into the brain by polysorbate 80 and sodium caprate. J Pharm Pharmacol 2001; 53: 149–54

    Article  PubMed  CAS  Google Scholar 

  129. Brouwer E, Verweij J, de Bruijn P, et al. Measurement of fraction unbound paclitaxel in human plasma. Drug Metab Dispos 2000; 28: 1141–5

    PubMed  CAS  Google Scholar 

  130. van Zuylen L, Karlsson MO, Verweij J, et al. Pharmacokinetic modeling of paclitaxel encapsulation in Cremophor EL micelles. Cancer Chemother Pharmacol 2001; 47: 309–18

    Article  PubMed  CAS  Google Scholar 

  131. Sonnichsen DS, Hurwitz CA, Pratt CB, et al. Saturable pharmacokinetics and paclitaxel pharmacodynamics in children with solid tumors. J Clin Oncol 1994; 12: 532–8

    PubMed  CAS  Google Scholar 

  132. Karlsson MO, Molnar V, Freijs A, et al. Pharmacokinetic models for the saturable distribution of paclitaxel. Drug Metab Dispos 1999; 27: 1220–3

    PubMed  CAS  Google Scholar 

  133. Henningsson A, Karlsson MO, Vigano L, et al. Mechanism-based pharmacokinetic model for paclitaxel. J Clin Oncol 2001; 19: 4065–73

    PubMed  CAS  Google Scholar 

  134. Kessel D. Properties of Cremophor EL micelles probed by fluorescence. Photochem Photobiol 1992; 56: 447–51

    Article  PubMed  CAS  Google Scholar 

  135. Holmes FA, Rowinsky EK. Pharmacokinetic profiles of doxorubicin in combination with taxanes. Semin Oncol 2001; 28 Suppl. 12: 8–14

    PubMed  CAS  Google Scholar 

  136. Holmes FA, Madden T, Newman RA, et al. Sequence-dependent alteration of doxorubicin pharmacokinetics by paclitaxel in a phase I study of paclitaxel and doxorubicin in patients with metastatic breast cancer. J Clin Oncol 1996; 14: 2713–21

    PubMed  CAS  Google Scholar 

  137. Vigano L, Locatelli A, Grasselli G, et al. Drug interactions of paclitaxel and docetaxel and their relevance for the design of combination therapy. Invest New Drugs 2001; 19: 179–96

    Article  PubMed  CAS  Google Scholar 

  138. Danesi R, Innocenti F, Fogli S, et al. Pharmacokinetics and pharmacodynamics of combination chemotherapy with paclitaxel and epirubicin in breast cancer patients. Br J Clin Pharmacol 2002; 53: 508–18

    Article  PubMed  CAS  Google Scholar 

  139. Fogli S, Danesi R, Gennari A, et al. Gemcitabine, epirubicin and paclitaxel: pharmacokinetic and pharmacodynamic interactions in advanced breast cancer. Ann Oncol 2002; 13: 919–27

    Article  PubMed  CAS  Google Scholar 

  140. Kasai T, Oka M, Soda H, et al. Phase I and pharmacokinetic study of paclitaxel and irinotecan for patients with advanced non-small cell lung cancer. Eur J Cancer 2002; 38: 1871–8

    Article  PubMed  CAS  Google Scholar 

  141. Lum BL, Kaubisch S, Yahanda AM, et al. Alteration of etoposide pharmacokinetics and pharmacodynamics by cyclosporine in a phase I trial to modulate multidrug resistance. J Clin Oncol 1992; 10: 1635–42

    PubMed  CAS  Google Scholar 

  142. Lacayo NJ, Lum BL, Becton DL, et al. Pharmacokinetic interactions of cyclosporine with etoposide and mitoxantrone in children with acute myeloid leukemia. Leukemia 2002; 16: 920–7

    Article  PubMed  CAS  Google Scholar 

  143. Rushing DA, Raber SR, Rodvold KA, et al. The effects of cyclosporine on the pharmacokinetics of doxorubicin in patients with small cell lung cancer. Cancer 1994; 74: 834–41

    Article  PubMed  CAS  Google Scholar 

  144. Samuels BL, Mick R, Vogelzang NJ, et al. Modulation of vinblastine resistance with cyclosporine: a phase I study. Clin Pharmacol Ther 1993; 54: 421–9

    Article  PubMed  CAS  Google Scholar 

  145. Boote DJ, Dennis IF, Twentyman PR, et al. Phase I study of etoposide with SDZ PSC 833 as a modulator of multidrug resistance in patients with cancer. J Clin Oncol 1996; 14: 610–8

    PubMed  CAS  Google Scholar 

  146. Minami H, Ohtsu T, Fujii H, et al. Phase I study of intravenous PSC-833 and doxorubicin: reversal of multidrug resistance. Jpn J Cancer Res 2001; 92: 220–30

    Article  PubMed  CAS  Google Scholar 

  147. Lunardi G, Venturini M, Vannozzi MO, et al. Influence of alternate sequences of epirubicin and docetaxel on the pharmacokinetic behaviour of both drugs in advanced breast cancer. Ann Oncol 2002; 13: 280–5

    Article  PubMed  CAS  Google Scholar 

  148. Esposito M, Venturini M, Vannozzi MO, et al. Comparative effects of paclitaxel and docetaxel on the metabolism and pharmacokinetics of epirubicin in breast cancer patients. J Clin Oncol 1999; 17: 1132–40

    PubMed  CAS  Google Scholar 

  149. Loos WJ, Baker SD, Verweij J, et al. Influence of polysorbate 80 on unbound fractions of anticancer agents [abstract]. Eur J Cancer 2002; S38 Suppl. 7: 111

    Google Scholar 

  150. Reynolds JA. The role of micelles in protein: detergent interactions. Methods Enzymol 1979; 61: 58–62

    Article  PubMed  CAS  Google Scholar 

  151. Guentert TW, Oie S, Paalzow L, et al. Interaction of mixed micelles formed from glycocholic acid and lecithin with the protein binding of various drugs. Br J Clin Pharmacol 1987; 23: 569–77

    Article  PubMed  CAS  Google Scholar 

  152. Petitpas I, Grune T, Bhattacharya AA, et al. Crystal structures of human serum albumin complexed with monounsaturated and polyunsaturated fatty acids. J Mol Biol 2001; 314: 955–60

    Article  PubMed  CAS  Google Scholar 

  153. McLeod HL, Kearns CM, Kuhn JG, et al. Evaluation of the linearity of docetaxel pharmacokinetics. Cancer Chemother Pharmacol 1998; 42: 155–9

    Article  PubMed  CAS  Google Scholar 

  154. Anderberg EK, Nystrom C, Artursson P. Epithelial transport of drugs in cell culture: VII. effects of pharmaceutical surfactant excipients and bile acids on transepithelial permeability in monolayers of human intestinal epithelial (Caco-2) cells. J Pharm Sci 1992; 81: 879–87

    Article  PubMed  CAS  Google Scholar 

  155. Oberle RL, Moore TJ, Krummel DA. Evaluation of mucosal damage of surfactants in rat jejunum and colon. J Pharmacol Toxicol Methods 1995; 33: 75–81

    Article  PubMed  CAS  Google Scholar 

  156. Masters JR, McDermott BJ, Jenkins WE, et al. ThioTEPA pharmacokinetics during intravesical chemotherapy and the influence of Tween 80. Cancer Chemother Pharmacol 1990; 25: 267–73

    Article  PubMed  CAS  Google Scholar 

  157. Nerurkar MM, Burton PS, Borchardt RT. The use of surfactants to enhance the permeability of peptides through Caco-2 cells by inhibition of an apically polarized efflux system. Pharm Res 1996; 13: 528–34

    Article  PubMed  CAS  Google Scholar 

  158. Cornaire G, Woodley JF, Saivin S, et al. Effect of polyoxyl 35 castor oil and Polysorbate 80 on the intestinal absorption of digoxin in vitro. Arzneimittel Forschung 2000; 50: 576–9

    PubMed  CAS  Google Scholar 

  159. Thiebaut F, Tsuruo T, Hamada H, et al. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci U S A 1987; 84:7735–8

    Article  PubMed  CAS  Google Scholar 

  160. van Asperen J, van Tellingen O, Beijnen JH. The pharmacological role of P-glycoprotein in the intestinal epithelium. Pharmacol Res 1998; 37: 429–35

    Article  PubMed  Google Scholar 

  161. Tayrouz Y, Ding R, Burhenne J, et al. Pharmacokinetic and pharmaceutic interaction between digoxin and Cremophor RH40. Clin Pharmacol Ther 2003; 73: 397–405

    Article  PubMed  CAS  Google Scholar 

  162. Malingre MM, Schellens JH, van Tellingen O, et al. The cosolvent Cremophor EL limits absorption of orally administered paclitaxel in cancer patients. Br J Cancer 2001; 85: 1472–7

    Article  PubMed  CAS  Google Scholar 

  163. Bardelmeijer HA, Ouwehand M, Malingre MM, et al. Entrapment by Cremophor EL decreases the absorption of paclitaxel from the gut. Cancer Chemother Pharmacol 2002; 49: 119–25

    Article  PubMed  CAS  Google Scholar 

  164. Martin-Facklam M, Burhenne J, Ding R, et al. Dose-dependent increase of saquinavir bioavailability by the pharmaceutic aid Cremophor EL. Br J Clin Pharmacol 2002; 53: 576–81

    Article  PubMed  CAS  Google Scholar 

  165. Schubiger G, Gruter J, Shearer MJ. Plasma vitamin K1 and PIVKA-II after oral administration of mixed- micellar or Cremophor EL-solubilized preparations of vitamin Kl to normal breast-fed newborns. J Pediatr Gastroenterol Nutr 1997; 24: 280–4

    Article  PubMed  CAS  Google Scholar 

  166. Redondo PA, Alvarez AI, Garcia JL, et al. Influence of surfactants on oral bioavailability of albendazole based on the formation of the sulphoxide metabolites in rats. Biopharm Drug Dispos 1998; 19: 65–70

    Article  PubMed  CAS  Google Scholar 

  167. Ford J, Woolfe J, Florence AT. Nanospheres of cyclosporin A: poor oral absorption in dogs. Int J Pharm 1999; 183: 3–6

    Article  PubMed  CAS  Google Scholar 

  168. Erlich L, Yu D, Pallister DA, et al. Relative bioavailability of danazol in dogs from liquid-filled hard gelatin capsules. Int J Pharm 1999; 179: 49–53

    Article  PubMed  CAS  Google Scholar 

  169. Jamali F, Axelson JE. Griseofulvin-phenobarbital interaction: a formulation-dependent phenomenon. J Pharm Sci 1978; 67: 466–70

    Article  PubMed  CAS  Google Scholar 

  170. Kim JY, Ku YS. Enhanced absorption of indomethacin after oral or rectal administration of a self-emulsifying system containing indomethacin to rats. Int J Pharm 2000; 194: 81–9

    Article  PubMed  CAS  Google Scholar 

  171. Yamamoto K, Shah AC, Nishihata T. Enhanced rectal absorption of itazigrel formulated with polysorbate 80 micelle vehicle in rat: role of co-administered esterase. J Pharm Pharmacol 1994; 46: 608–11

    Article  PubMed  CAS  Google Scholar 

  172. Allen Jr LV, Levinson RS, Robinson C, et al. Effect of surfactant on tetra-cycline absorption across everted rat intestine. J Pharm Sci 1981; 70: 269–71

    Article  PubMed  CAS  Google Scholar 

  173. Meerum-Terwogt JM, Malingre MM, Beijnen JH, et al. Coadministration of oral cyclosporin A enables oral therapy with paclitaxel. Clin Cancer Res 1999; 5: 3379–84

    PubMed  CAS  Google Scholar 

  174. Meerum-Terwogt JM, Beijnen JH, ten Bokkel Huinink WW, et al. Co-administration of cyclosporin enables oral therapy with paclitaxel [letter]. Lancet 1998; 352: 285

    Article  PubMed  CAS  Google Scholar 

  175. Malingre MM, Meerum-Terwogt JM, Beijnen JH, et al. Phase I and pharmacokinetic study of oral paclitaxel. J Clin Oncol 2000; 18: 2468–75

    PubMed  CAS  Google Scholar 

  176. Britten CD, Baker SD, Denis LJ, et al. Oral paclitaxel and concurrent cyclosporin A: targeting clinically relevant systemic exposure to paclitaxel. Clin Cancer Res 2000; 6: 3459–68

    PubMed  CAS  Google Scholar 

  177. Malingre MM, Beijnen JH, Schellens JH. Oral delivery of taxanes. Invest New Drugs 2001; 19: 155–62

    Article  PubMed  CAS  Google Scholar 

  178. Malingre MM, Beijnen JH, Rosing H, et al. A phase I and pharmacokinetic study of bi-daily dosing of oral paclitaxel in combination with cyclosporin A. Cancer Chemother Pharmacol 2001; 47: 347–54

    Article  PubMed  CAS  Google Scholar 

  179. Malingre MM, Richel DJ, Beijnen JH, et al. Coadministration of cyclosporine strongly enhances the oral bioavailability of docetaxel. J Clin Oncol 2001; 19: 1160–6

    PubMed  CAS  Google Scholar 

  180. Dolan ME, Pegg AE, Moschel RC, et al. Biodistribution of O6-benzylguanine and its effectiveness against human brain tumor xenografts when given in polyethylene glycol or Cremophor EL. Cancer Chemother Pharmacol 1994; 35:121–6

    Article  PubMed  CAS  Google Scholar 

  181. Knemeyer I, Wientjes MG, Au JL. Cremophor reduces paclitaxel penetration into bladder wall during intravesical treatment. Cancer Chemother Pharmacol 1999; 44: 241–8

    Article  PubMed  CAS  Google Scholar 

  182. Markman M. Intraperitoneal chemotherapy in the treatment of ovarian cancer. Ann Med 1996; 28: 293–6

    Article  PubMed  CAS  Google Scholar 

  183. ten Tije BJ, Wils J. Intraperitoneal cisplatin in the treatment of refractory or recurrent advanced ovarian carcinoma. Oncology 1992; 49: 442–4

    Article  PubMed  Google Scholar 

  184. Markman M, Rowinsky E, Hakes T, et al. Intraperitoneal administration of Taxol in the management of ovarian cancer. J Natl Cancer Inst Monogr 1993 15: 103–6

    PubMed  Google Scholar 

  185. Nuijen B, Bouma M, Schellens JH, et al. Progress in the development of alternative pharmaceutical formulations of taxanes. Invest New Drugs 2001; 19: 143–53

    Article  PubMed  CAS  Google Scholar 

  186. Fumoleau P, Tubiana-Hulin M, Soulie P, et al. A dose finding and pharmacokinetic (PK) phase I study of a new formulation of docetaxel (D) in advanced solid tumors [abstract]. Ann Oncol 1998; 9 Suppl. 2: 101

    Google Scholar 

  187. Ibrahim NK, Desai N, Legha S, et al. Phase I and pharmacokinetic study of ABI-007, a Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. Clin Cancer Res 2002; 8: 1038–44

    PubMed  CAS  Google Scholar 

  188. Dosio F, Arpicco S, Brusa P, et al. Poly(ethylene glycol)-human serum albumin-paclitaxel conjugates: preparation, characterization and pharmacokinetics. J Control Release 2001; 76: 107–17

    Article  PubMed  CAS  Google Scholar 

  189. Spigel SC, Jones SF, Greco FA, et al. S-8148 vitamin E paclitaxel emulsion: preclinical and phase 1 data [abstract]. Proc Am Soc Clin Oncol 2002; 21: 406

    Google Scholar 

  190. Rodrigues DG, Covollan CC, Coradil S, et al. Use of a cholesterol-rich emulsion that binds to low-density lipoprotein receptors as carrier for paclitaxel. Clin Cancer Res 2001; 7 Suppl. 1: 111

    Google Scholar 

  191. Bowden C, Huang C, Eisenberg D, et al. Phase 1 trial in advanced malignancies with liposome encapsulated paclitaxel (LEP) Q 3 weeks [abstract]. Proc Am Soc Clin Oncol 2002; 21: 1862

    Google Scholar 

  192. Alcaro S, Ventura CA, Paolino D, et al. Preparation, characterization, molecular modeling and in vitro activity of paclitaxelcyclodextrin complexes. Bioorg Med Chem Lett 2002; 12: 1637–41

    Article  PubMed  CAS  Google Scholar 

  193. Damascelli B, Cantu G, Mattavelli F, et al. Intraarterial chemotherapy with polyoxyethylated castor oil free paclitaxel, incorporated in albumin nanoparticles (ABI-007): phase II study of patients with squamous cell carcinoma of the head and neck and anal canal: preliminary evidence of clinical activity. Cancer 2001; 92: 2592–602

    Article  PubMed  CAS  Google Scholar 

  194. Harper E, Dang W, Lapidus RG, et al. Enhanced efficacy of a novel controlled release paclitaxel formulation (PACLIMER delivery system) for local-regional therapy of lung cancer tumor nodules in mice. Clin Cancer Res 1999; 5: 4242–8

    PubMed  CAS  Google Scholar 

  195. Hidalgo M, Aylesworth C, Hammond LA, et al. Phase I and pharmacokinetic study of BMS-184476, a taxane with greater potency and solubility than paclitaxel. J Clin Oncol 2001; 19: 2493–503

    PubMed  CAS  Google Scholar 

  196. Rose WC, Long BH, Fairchild CR, et al. Preclinical pharmacology of BMS-275183, an orally active taxane. Clin Cancer Res 2001; 7: 2016–21

    PubMed  CAS  Google Scholar 

  197. Nicoletti MI, Colombo T, Rossi C, et al. IDN5109, a taxane with oral bioavailability and potent antitumor activity. Cancer Res 2000; 60: 842–6

    PubMed  CAS  Google Scholar 

  198. Gelmon KA, Latreille J, Tolcher A, et al. Phase I dose-finding study of a new taxane, RPR 109881 A, administered as a one-hour intravenous infusion days 1 and 8 to patients with advanced solid tumors. J Clin Oncol 2000; 18: 4098–08

    PubMed  CAS  Google Scholar 

  199. Sparreboom A, Wolff AC, Verweij J, et al. Disposition of DHA-paclitaxel, a novel taxane, in blood: in vitro and clinical pharmacokinetic studies. Clin Cancer Res 2003; 9: 151–9

    PubMed  CAS  Google Scholar 

  200. Bradley MO, Webb NL, Anthony FH, et al. Tumor targeting by covalent conjugation of a natural fatty acid to paclitaxel. Clin Cancer Res 2001; 7: 3229–38

    PubMed  CAS  Google Scholar 

  201. Meerum-Terwogt JM, ten Bokkel Huinink WW, Schellens JH, et al. Phase I clinical and pharmacokinetic study of PNU166945, a novel water-soluble polymer-conjugated prodrug of paclitaxel. Anticancer Drugs 2001; 12: 315–23

    Article  PubMed  CAS  Google Scholar 

  202. Todd R, Boddy AV, Verril M, et al. Phase I and pharmalogical study of CT-2103, a poly(L-glutamic acid)-paclitaxel conjugate [abstract]. Clin Cancer Res 2001; 7 Suppl. 1: 115

    Google Scholar 

  203. Kruijtzer CM, Schellens JH, Mezger J. Phase II and pharmacologic study of weekly oral paclitaxel plus cyclosporine in patients with advance non-small cell lung cancer. J Clin Oncol 2002; 20: 4508–16

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript. The authors have no potential conflicts of interest that are directly relevant to the contents of this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alex Sparreboom.

Rights and permissions

Reprints and permissions

About this article

Cite this article

ten Tije, A.J., Verweij, J., Loos, W.J. et al. Pharmacological Effects of Formulation Vehicles. Clin Pharmacokinet 42, 665–685 (2003). https://doi.org/10.2165/00003088-200342070-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-200342070-00005

Keywords

Navigation