Estimation of the Rates of Available Fraction for Some 4-Substituted Acetophenone Derivatives in the Rat Reversible Drug-Metabolite Pharmacokinetics

• Published in: Chemical & pharmaceutical bulletin Vol. 36; no. 11; pp. 4612 - 4618
• Main Authors: NAGAMINE, SACHIKO, OTAWA, TOMOKO, NAKAE, HIROKO, ASADA, SHOZO
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.11.1988; Maruzen
• Subjects: 4-substituted acetophenone; Acetophenones - pharmacokinetics; Animals; AUC; Biological and medical sciences; fundamental clearance; hepatic available fraction; interconversion model; Male; Medical sciences; metabolite pharmacokinetics; Pharmacology. Drug treatments; portal vein administration; Rats; Rats, Inbred Strains; reversible metabolism
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.36.4612

4-Acetamidoacetophenone (Ia), 4-acetylbenzenesulfonamide (IIa) and acetohexamide (IIIa) and the respective reduced compounds, 4-substituted α-hydroxyethylphenyl derivatives, are in a reversible drug-metabolite relationship in rats. The pharmacokinetic profiles of these agents were studied after intraportal (pv) administration in comparison with those after intravenous (iv) administration using an interconversion model. Fundamental clearances, CL10, CL12, CL20 and CL21, were calculated using four AUC (area under the plasma concentration-time curve) values obtained after iv administration of the drug and preformed metabolite. The hepatic available fraction of parent drug, FH1 and sequential hepatic available fraction of its metabolite, FH2 were estimated by the following equations.