TY - JOUR T1 - PHARMACOKINETIC STUDIES OF THE DISPOSITION OF SECOBARBITAL IN THE DOG JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 513 LP - 520 VL - 2 IS - 6 AU - RICHARD O. MUHLHAUSER AU - W. DAVID WATKINS AU - ROBERT C. MURPHY AU - CHARLES A. CHIDSEY Y1 - 1974/11/01 UR - http://dmd.aspetjournals.org/content/2/6/513.abstract N2 - The fate of a large intravenous dose of secobarbital (36 mg/kg) was studied with use of 14C-labeled drug to quantify its metabolism and disposition in a canine model of human overdose. Secobarbital disappeared from plasma as a first order process with a rate constant of 0.08 hr-1, which represented predominantly metabolic clearance averaging 21.6 ml/min. The primary metabolites were (ω -1)-hydroxysecobarbital (36.5%) and dihydroxydihydrosecobarbital (secodiol, 15.7%), both of which were excreted also as glucuronide conjugates (26.2%). Pretreatment with pentobarbital stimulated the rate of metabolism markedly but did not significantly affect the relative rates of formation of the individual metabolites. No evidence was obtained for an altered distribution of metabolism of this large quantity of drug over the total period of its removal; this implies an absence of saturation kinetics in either hydroxylation pathway. Copyright © 1974 by The American Society for Pharmacology and Experimental Therapeutics ER -