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- W1974097103 abstract "The purpose of this study was to define the pharmacokinetics of diazepam in monkeys following an im injection of 100 μg/kg (the minimum effective dose that prevents nerve agent-induced convulsions in pyridostjgmine-pretreated, atropine- and 2-PAM-treated monkeys) in order to predict what im dose in humans is needed to prevent nerve agent-induced convulsions. Six rhesus monkeys were administered diazepam in the hind limb. Blood (3 mL) was collected via an indwelling saphenous catheter immediately prior to and 5,10, 15, 25, 40, 60, 90, 120,180, and 240 min after diazepam dosing. A contract laboratory, blind to the labeling code, analyzed diazepam serum concentrations by electron-capture gas chromatography and the percentage of unbound diazepam by equilibrium dialysis. The concentration-time data for total (unbound and bound) diazepam individually determined for each animal was best described by a one-compartment open model with first-order absorption and elimination. The average maximum serum concentration (50 ng/mL) was reached in 29 min. The volume of distribution and systemic clearance, assuming 100% bioavailability, were 1.5 L/kg and 19.4 mL/min/kg, respectively. The percentage of diazepam unbound to serum proteins was 4.6% and, therefore, the maximum concentration of free diazepam was 2.3 ng/mL. These results, when compared with human pharmacokinetic studies, allow a means of extrapolating effective monkey anticonvulsant doses to humans on a pharmacokinetic basis." @default.
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- W1974097103 date "1991-10-01" @default.
- W1974097103 modified "2023-09-23" @default.
- W1974097103 title "Pharmacokinetics of Diazepam Intramuscularly Administered to Rhesus Monkeys" @default.
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- W1974097103 doi "https://doi.org/10.1002/jps.2600801003" @default.
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