Pharmacokinetics of sodium borocaptate: a critical assessment of dosing paradigms for boron neutron capture therapy

Summary The pharmacokinetics of sodium borocaptate (BSH), a drug that has been used clinically for boron neutron capture therapy (BNCT) of malignant brain tumors, have been characterized by measuring boron concentrations by direct current plasma-atomic emission spectroscopy (DCP-AES) in a group of 23 patients with high-grade gliomas. The disposition of BSH following intravenous (i.v.) infusion, which was determined by measuring plasma boron concentrations by DCP-AES, was consistent with a three-compartment open model with zero-order input and first-order elimination from the central compartment. Boron disposition was linear over the dose range of 26.5–88.2 mg BSH/kg body weight (b.w.), corresponding to 15–50 mg boron/kg b.w. Mean total body boron plasma clearance was 14.4 ± 3.5 ml/min and the harmonic mean half-lives (range) were 0.6 (0.3–3.7), 6.5 (4.8–10.1) and 77.8 (49.6–172.0) h for theα, β, andγ disposition phases, respectively. Using an empirically determined plasma: blood boron concentration ratio of 1.3 ± 0.2, the calculated total body boron blood clearance was 18.5 ± 4.5 ml/min. In order to develop a model for selecting the optimum dosing paradigm, a pharmacokinetic correlation was established between the boron content of normal brain, solid tumor, and infiltrating tumor to the shallow tissue pharmacokinetic compartment (C₂). Based on our model, it was concluded that although multiple i.v. infusions of BSH might increase absolute tumor boron concentrations, they will not improve the tumor: plasma boron concentration ratios over those attainable by a single i.v. infusion. The results from our study are confirmatory of those previously reported by others when blood sampling has been carried out for a sufficient period of time to adequately characterize the pharmacokinetics.