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The Stereoselective Pharmacokinetics of Etodolac in Young and Elderly Subjects, and After Cholecystectomy
Author(s) -
Brocks Dion R.,
Jamali Fakhreddin,
Russell Anthony S.,
Skeith Kenneth J.
Publication year - 1992
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1992.tb03799.x
Subject(s) - etodolac , pharmacokinetics , volume of distribution , stereoselectivity , enantiomer , chemistry , pharmacology , medicine , stereochemistry , biochemistry , catalysis
The pharmacokinetics of the enantiomers of etodolac were studied in six young subjects (ages 28 ± 3.3 years), 6 nonarthritic elderly subjects (ages 73 ± 6.0 years), and in three cholecystectomy patients after single oral doses of the racemate (200 mg). In all subjects, the plasma concentrations of R‐etodolac, which is pharmacologically inactive, greatly exceeded those of the pharmacologically active S‐enantiomer. Stereoselectivity was reflected in the pharmacokinetics, with R > S for maximum peak plasma concentration and area under the concentration versus time curve, and S > R for apparent oral clearance and apparent volume of distribution. On average, less than 25% of the dose of each enantiomer was excreted in the urine within 24 hours as alkali‐labile conjugates; little or no unchanged drug was recovered. Bile constituted a minor route of elimination of etodolac as conjugated enantiomers. There were no significant differences in the pharmacokinetics of etodolac enantiomers between the young and elderly subjects. The results reflect the importance of considering stereoselectivity in evaluating the pharmacokinetics of etodolac.