Kiger, W. S., III, Palmer, M. R., Riley, K. J., Zamenhof, R. G. and Busse, P. M. A Pharmacokinetic Model for the Concentration of ¹⁰B in Blood after Boronophenylalanine- Fructose Administration in Humans.

An open two-compartment model has been developed for predicting ¹⁰B concentrations in blood after intravenous infusion of the l-p-boronophenylalanine-fructose complex (BPA-F) in humans and derived from studies of pharmacokinetics in 24 patients in the Harvard-MIT Phase I clinical trials of BNCT. The ¹⁰B concentration profile in blood exhibits a characteristic rise during the infusion to a peak of ∼32 μg/g (for infusion of 350 mg/kg over 90 min) followed by a biphasic exponential clearance profile with half-lives of 0.34 ± 0.12 and 9.0 ± 2.7 h, due to redistribution and primarily renal elimination, respectively. The model rate constants k₁, k₂ and k₃ are 0.0227 ± 0.0064, 0.0099 ± 0.0027 and 0.0052 ± 0.0016 min^–1, respectively, and the central compartment volume of distribution, V₁, is 0.235 ± 0.042 kg/kg. The validity of this model was demonstrated by successfully predicting the average pharmacokinetic response for a cohort of patients who were administered BPA-F using an infusion schedule different from those used to derive the parameters of the model. Furthermore, the mean parameters of the model do not differ for cohorts of patients infused using different schedules.