Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
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The pharmacokinetic profile of progabide was investigated in five chronically catheterized male rhesus monkeys. The experimental design included single-dose intravenous bolus and oral administration at two dose levels (50 and 100 mg) and zero-order intravenous infusion for 7 days. Plasma samples were analyzed by electron-capture-GLC. Protein binding of the drug was determined by equilibrium dialysis (4 degrees). A one-compartment open model with monoexponential decay was proposed to describe the pharmacokinetics. The mean parameters (+/-SEM) of the 50- and 100-mg iv bolus were: total body clearance, 2.09 (+/-0.15) and 1.53 (+/-0.18) liter/hr/kg; half-life, 0.656 (+/-0.054) and 0.789 (+/-0.079) hr; distribution volume, 1.97 (+/-0.08) and 1.79 (+/-0.21) liter/kg. Progabide was highly bound to plasma proteins and also to erythrocytes. The drug was rapidly absorbed (Tmax less than 1 hr at both doses). The mean bioavailability was attributed principally to a first-pass effect. In the constant rate infusion study, systemic clearance was larger than that of the single dose studies.
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PMID:Pharmacokinetic profile of progabide, a new gamma-aminobutyric acid-mimetic drug, in rhesus monkey. 709 24