Pharmacokinetic Properties of Ethosuximide in Monkeys. II. Chronic Intravenous and Oral Administration

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Abstract
Three types of chronic-dosing experiments were implemented in a group of chronically catheterized male rhesus monkeys: Study I, constant rate infusion; Study II, infusion at 3 consecutive rates with priming doses and Study III, oral multiple dosing at 2 consecutive levels with priming doses. Zero-order infusion rates and priming and maintenance doses were calculated for each animal using individual single-dose pharmacokinetic parameters. Ethosuximide was measured in plasma and urine by GLC. Experimental and predicted plasma and urine levels were in good agreement for all three studies. Total body clearance (Studies I and II) and elimination half-life (Studies I, II, and III) were not significantly different from their respective single-dose values. Excretion rate was proportional to infusion rate (Study II) and maintenance dose (Study III). In the case of ethosuximide in monkey, pharmacokinetic parameters derived from single-dose studies can be used to predict multiple-dosing schedules.