Biopharmaceutical studies on drug/conjugated-metabolite interactions. III. Effect of acetaminophen sulfate and its positional isomers on the pharmacokinetics of acetaminophen in rats

Biological & Pharmaceutical Bulletin
T NakayamaT Kimura

Abstract

The effect of three positional isomers, o-, m- and p-acetylaminophenyl sulfate (AOAPS, AMAPS and APAPS (acetaminophen sulfate), respectively), on the pharmacokinetics of acetaminophen (APAP) was investigated in rats. All of the intravenously administered positional isomers were rapidly eliminated from plasma, and approximately 80% of the dose was excreted in an unchanged form in the urine within 4 h, while biliary excretions represented a small percent of the doses. Following the intravenous bolus injection of APAP, plasma elimination of APAP was accelerated and the distribution volume of APAP was increased under a steady state concentration (about 10 microg APAP eq/ml) of AOAPS or APAPS, but not AMAPS, as compared with saline infusion. Total body clearances of APAP were increased from 18.3 ml/min/kg for the control to 23.9 and 26.9 ml/min/kg for AOAPS and APAPS coadministration, respectively. AOAPS and APAPS competitively displaced the serum protein binding of APAP, while AMAPS had little effect. The distribution volume of unbound APAP was anomalously increased by APAPS, while it was not affected by AOAPS or AMAPS. Tissue-to-plasma concentration ratios of APAP were significantly increased by APAPS in the liver, kidney and brai...Continue Reading

Citations

Jan 10, 2002·Journal of Pharmaceutical Sciences·Patrick Poulin, Frank-Peter Theil
May 31, 2001·Biological & Pharmaceutical Bulletin·Y OhkawaT Nakayama
Jan 5, 2002·Biological & Pharmaceutical Bulletin·Y OhkawaT Nakayama
Jun 26, 2002·Biological & Pharmaceutical Bulletin·Yuhsuke OhkawaTaiji Nakayama
Jul 19, 2012·Biopharmaceutics & Drug Disposition·Soo Hyun LeeByung Hwa Jung

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