Distribution and excretion of boron after intravenous administration of disodium mercaptoundecahydro-closo-dodecaborate to rats.
Disodium mercaptoundecahydro-closo-dodecaborate (BSH) is an important compound for boron neutron capture therapy. The pharmacokinetics of boron by BSH were studied in normal rats after rapid intravenous injection at three doses (30, 100, 300 mg/kg) or continuous infusion (100 mg/kg/30 min). The boron concentration in biological samples was measured by inductively coupled plasma atomic emission spectroscopy. The blood half-lives of boron in the elimination phase (t1/2 beta) after rapid injection of BSH at doses of 30, 100 and 300 mg/kg were 1.7, 17 and 19 hr, respectively. AUC (32, 219 and 4030 micrograms.hr/ml) increased with the dose, but there was no proportionality among the values. Total clearance decreased drastically from 233 ml/hr/kg (100 mg/kg) to 38 ml/hr/kg (300 mg/kg). As boron was excreted mainly into urine, these results suggest that renal function failure might occur with dosing of 300 mg/kg. In the case of continuous infusion of 100 mg/kg of BSH for 30 min, the pharmacokinetic parameters were similar to those of rapid injection of 100 mg/kg. The highest boron concentration was observed in the kidney and the lowest in the brain. After multiple dosing of BSH at 100 mg/kg/day x 14 days, the boron concentrations in blood, liver, lung and kidney at 24 hr after the last dosing were higher than those after single dosing and were similar to those of simulated values calculated from the single dosing parameters. These results clearly indicated that boron does not accumulate unexpectedly in any tissue with multiple dosing of 100 mg/kg of BSH for two weeks.
Yamaguchi
T
T
Developmental Research Laboratories, Shionogi & Co. Ltd., Osaka, Japan.
Nakajima
Y
Y
Miyamoto
H
H
Mizobuchi
M
M
Kanazu
T
T
Kadono
K
K
Nakamoto
K
K
Ikeuchi
I
I
D000818:Animals; D001894:Borohydrides / Q000008:administration & dosage / Q000378:metabolism*; D001895:Boron / Q000493:pharmacokinetics* / Q000652:urine; D001921:Brain / Q000378:metabolism; D006207:Half-Life; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000378:metabolism*
D001894:Borohydrides; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D001895:Boron