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Stereoselective pharmacokinetics of ketoprofen in the rat. Influence of route of administration.
Drug Metab Dispos. 1988 Jul-Aug; 16(4):623-6.DM

Abstract

The 2-arylpropionic acid nonsteroidal anti-inflammatory drugs are usually administered as racemates. The enantiomers may have different pharmacokinetics and the R-isomer may metabolically invert to the S-isomer. To pinpoint the kinetics of the inversion and the location in which this metabolic process takes place, racemic ketoprofen (KT) was administered to the rat. Using a stereospecific HPLC assay, the pharmacokinetics of KT were studied following 10 mg/kg iv, po, and ip doses of racemic KT to male Sprague-Dawley rats. Plasma concentrations were always greater for (S)-KT than for (R)-KT. The mean +/- SD AUC S/R ratios were 11.8 +/- 9.93 (N = 5), 11.0 +/- 2.64 (N = 4), and 33.7 +/- 11.2 (N = 5) after iv, ip, and po doses, respectively. Bile duct-cannulated rats (N = 4) had AUCs of 85.4 +/- 58.6 and 22.8 +/- 18.4 (mg/liter) hr for (S)- and (R)-KT, respectively. The percentage of conjugated drug recovered in bile was 77.9 +/- 3.77 and 11.4 +/- 2.48% of the dose as (S)- and (R)-KT, respectively. The data indicate 1) substantial stereoselectivity, 2) presystemic gastrointestinal and systemic inversion of (R)- to (S)-KT, 3) extensive elimination of drug through bile in rats, and 4) extensive reabsorption subsequent to biliary excretion.

Authors+Show Affiliations

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

2903033

Citation

Foster, R T., and F Jamali. "Stereoselective Pharmacokinetics of Ketoprofen in the Rat. Influence of Route of Administration." Drug Metabolism and Disposition: the Biological Fate of Chemicals, vol. 16, no. 4, 1988, pp. 623-6.
Foster RT, Jamali F. Stereoselective pharmacokinetics of ketoprofen in the rat. Influence of route of administration. Drug Metab Dispos. 1988;16(4):623-6.
Foster, R. T., & Jamali, F. (1988). Stereoselective pharmacokinetics of ketoprofen in the rat. Influence of route of administration. Drug Metabolism and Disposition: the Biological Fate of Chemicals, 16(4), 623-6.
Foster RT, Jamali F. Stereoselective Pharmacokinetics of Ketoprofen in the Rat. Influence of Route of Administration. Drug Metab Dispos. 1988 Jul-Aug;16(4):623-6. PubMed PMID: 2903033.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stereoselective pharmacokinetics of ketoprofen in the rat. Influence of route of administration. AU - Foster,R T, AU - Jamali,F, PY - 1988/7/1/pubmed PY - 1988/7/1/medline PY - 1988/7/1/entrez SP - 623 EP - 6 JF - Drug metabolism and disposition: the biological fate of chemicals JO - Drug Metab Dispos VL - 16 IS - 4 N2 - The 2-arylpropionic acid nonsteroidal anti-inflammatory drugs are usually administered as racemates. The enantiomers may have different pharmacokinetics and the R-isomer may metabolically invert to the S-isomer. To pinpoint the kinetics of the inversion and the location in which this metabolic process takes place, racemic ketoprofen (KT) was administered to the rat. Using a stereospecific HPLC assay, the pharmacokinetics of KT were studied following 10 mg/kg iv, po, and ip doses of racemic KT to male Sprague-Dawley rats. Plasma concentrations were always greater for (S)-KT than for (R)-KT. The mean +/- SD AUC S/R ratios were 11.8 +/- 9.93 (N = 5), 11.0 +/- 2.64 (N = 4), and 33.7 +/- 11.2 (N = 5) after iv, ip, and po doses, respectively. Bile duct-cannulated rats (N = 4) had AUCs of 85.4 +/- 58.6 and 22.8 +/- 18.4 (mg/liter) hr for (S)- and (R)-KT, respectively. The percentage of conjugated drug recovered in bile was 77.9 +/- 3.77 and 11.4 +/- 2.48% of the dose as (S)- and (R)-KT, respectively. The data indicate 1) substantial stereoselectivity, 2) presystemic gastrointestinal and systemic inversion of (R)- to (S)-KT, 3) extensive elimination of drug through bile in rats, and 4) extensive reabsorption subsequent to biliary excretion. SN - 0090-9556 UR - https://www.unboundmedicine.com/medline/citation/2903033/Stereoselective_pharmacokinetics_of_ketoprofen_in_the_rat__Influence_of_route_of_administration_ L2 - http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2903033 DB - PRIME DP - Unbound Medicine ER -