A pharmacokinetic model for the concentration of B-10 in blood after boronophenylalanine-fructose administration in humans

An open two-compartment model has been developed for predicting B-10 concen trations in blood after intravenous infusion of the L-p-boronophenylalanine -fructose complex (BPA-F) in humans and derived from studies of pharmacokin etics in 24 patients in the Harvard-MIT Phase I clinical trials of BNCT, Th e B-10 concentration profile in blood exhibits a characteristic rise during the infusion to a peak of similar to 32 mug/g (for infusion of 350 mg/kg o ver 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 primari ly renal elimination, respectively. The model rate constants k(1), k(2) and k(3) are 0.0227 +/- 0,0064, 0.0099 +/- 0.0027 and 0.0052 +/- 0.0016 min(-1 ), respectively, and the central compartment volume of distribution, V-1, i s 0.235 +/- 0.042 kg/kg, The validity of this model was demonstrated by suc cessfully predicting the average pharmacokinetic response for a cohort of p atients who were administered BPA-F using an infusion schedule different fr om 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. (C) 2001 by Radiation Research Society.