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

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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, CL_<10>, CL_<12>, CL_<20> and CL_<21>, 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, F_<H1> and sequential hepatic available fraction of its metabolite, F_<H2> were estimated by the following equations.F_d=(AUC^D_<pv>_D/dose^D_<pv>)/(AUC^D_<iv>_D/dose^D_<iv>)=F_<H1>+(1-F_<H1>)F_<H2>CL<21>/(CL_<20>+CL_<21>)F_m=(AUC^D_<pv>_M/dose^D_<pv>)/(AUC^D_<iv>_M/dose^D_<iv>)=F_<H1>+(1-F_<H_1>)F<H2>(CL_<10>+CL_<12>)/CL_<12>
公益社団法人日本薬学会の論文
1988-11-25