Pharmacokinetics of sodium mercaptoundecahydrododecaborate after intravenous injection in rats.

Boron neutron capture therapy (BNCT) is a binary therapy aimed at treating various forms of cancer. Sodium mercaptoundecahydrododecaborate (Na2B12H11SH) or BSH is the compound most widely used for BNCT. The pharmacokinetics of BSH were studied in rats after intravenous bolus injection at two doses of BSH (50 mg/kg and 100 mg/kg). BSH was analyzed by a high performance liquid chromatography (HPLC) method specific to BSH. The elimination of BSH from plasma was slow; the average elimination half life was approximately 15 hr for both doses. Estimates of the steady state volume of distribution and total clearance were 2.11 +/- 0.49 liters/kg and 0.28 +/- 0.03 liters/hr/kg, respectively, for the 50 mg/kg dose and 2.06 +/- 0.38 liters/kg and 0.32 +/- 0.06 liters/hr/kg, respectively, for the 100 mg/kg dose. The differences in the mean values of the parameters for the two doses were not statistically significant; this indicates that BSH exhibits linear pharmacokinetics over the dose range studied. BSH was moderately bound to plasma proteins and the binding was linear over the concentration range studied. Approximately 60% of the drug was recovered unchanged in urine after 24 hr. When we compared our results with the limited data available in the literature on BSH disposition in rats with use of nonspecific analysis methods, it seems that the BSH disposition determined by our HPLC method is not likely to be different from the total boron disposition measured by other methods.