Tags

Type your tag names separated by a space and hit enter

Stereoselective disposition of tiaprofenic acid enantiomers in rats.
Chirality. 1999; 11(2):103-8.C

Abstract

The pharmacokinetics and metabolic chiral inversion of the S(+)- and R(-)-enantiomers of tiaprofenic acid (S-TIA, R-TIA) were assessed in vivo in rats, and in addition the biochemistry of inversion was investigated in vitro in rat liver homogenates. Drug enantiomer concentrations in plasma were investigated following administration of S-TIA and R-TIA (i.p. 3 and 9 mg/kg) over 24 hr. Plasma concentrations of TIA enantiomers were determined by stereospecific HPLC analysis. After administration of R-TIA it was found that 1) there was a time delay of peak S-TIA plasma concentrations, 2) S-TIA concentrations exceeded R-TIA concentrations from approximately 2 hr after dosing, 3) Cmax and AUC(0-infinity) for S-TIA were greater than for R-TIA following administration of S-TIA, and 4) inversion was bidirectional but favored inversion of R-TIA to S-TIA. Bidirectional inversion was also observed when TIA enantiomers were incubated with liver homogenates up to 24 hr. However, the rate of inversion favored transformation of the R-enantiomer to the S-enantiomer. In conclusion, stereoselective pharmacokinetics of R- and S-TIA were observed in rats and bidirectional inversion in rat liver homogenates has been demonstrated for the first time. Chiral inversion of TIA may involve metabolic routes different from those associated with inversion of other 2-arylpropionic acids such as ibuprofen.

Authors+Show Affiliations

Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9951401

Citation

Erb, K, et al. "Stereoselective Disposition of Tiaprofenic Acid Enantiomers in Rats." Chirality, vol. 11, no. 2, 1999, pp. 103-8.
Erb K, Brugger R, Williams K, et al. Stereoselective disposition of tiaprofenic acid enantiomers in rats. Chirality. 1999;11(2):103-8.
Erb, K., Brugger, R., Williams, K., & Geisslinger, G. (1999). Stereoselective disposition of tiaprofenic acid enantiomers in rats. Chirality, 11(2), 103-8.
Erb K, et al. Stereoselective Disposition of Tiaprofenic Acid Enantiomers in Rats. Chirality. 1999;11(2):103-8. PubMed PMID: 9951401.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stereoselective disposition of tiaprofenic acid enantiomers in rats. AU - Erb,K, AU - Brugger,R, AU - Williams,K, AU - Geisslinger,G, PY - 1999/2/10/pubmed PY - 1999/2/10/medline PY - 1999/2/10/entrez SP - 103 EP - 8 JF - Chirality JO - Chirality VL - 11 IS - 2 N2 - The pharmacokinetics and metabolic chiral inversion of the S(+)- and R(-)-enantiomers of tiaprofenic acid (S-TIA, R-TIA) were assessed in vivo in rats, and in addition the biochemistry of inversion was investigated in vitro in rat liver homogenates. Drug enantiomer concentrations in plasma were investigated following administration of S-TIA and R-TIA (i.p. 3 and 9 mg/kg) over 24 hr. Plasma concentrations of TIA enantiomers were determined by stereospecific HPLC analysis. After administration of R-TIA it was found that 1) there was a time delay of peak S-TIA plasma concentrations, 2) S-TIA concentrations exceeded R-TIA concentrations from approximately 2 hr after dosing, 3) Cmax and AUC(0-infinity) for S-TIA were greater than for R-TIA following administration of S-TIA, and 4) inversion was bidirectional but favored inversion of R-TIA to S-TIA. Bidirectional inversion was also observed when TIA enantiomers were incubated with liver homogenates up to 24 hr. However, the rate of inversion favored transformation of the R-enantiomer to the S-enantiomer. In conclusion, stereoselective pharmacokinetics of R- and S-TIA were observed in rats and bidirectional inversion in rat liver homogenates has been demonstrated for the first time. Chiral inversion of TIA may involve metabolic routes different from those associated with inversion of other 2-arylpropionic acids such as ibuprofen. SN - 0899-0042 UR - https://www.unboundmedicine.com/medline/citation/9951401/Stereoselective_disposition_of_tiaprofenic_acid_enantiomers_in_rats_ L2 - https://doi.org/10.1002/(SICI)1520-636X(1999)11:2<103::AID-CHIR4>3.0.CO;2-1 DB - PRIME DP - Unbound Medicine ER -