PMID: 8592665Nov 1, 1995Paper

The problem of racemization in the stereospecific assay and pharmacokinetic evaluation of ketorolac in human and rats

Pharmaceutical Research
M VakilyF Jamali

Abstract

A comparison of a previously reported indirect (precolumn derivatization) assay for ketorolac (KT) and a new direct method described here was made to establish the conditions under which KT may undergo racemization and to explain the observed discrepancies in the pharmacokinetics of KT reported in the literature. A previously reported pre-column derivatization method and a new direct method were employed to determine the effect of pH and ionic strength on racemization. Using the conditions where no racemization occurred, the pharmacokinetics in humans and rats, and protein binding of KT enantiomers were determined. Under the chromatographic conditions employed for the direct assay, no racemization was observed. Under high pH and ionic strength, however, both methods resulted in KT racemization. The indirect method resulted in rapid and complete racemization due to the strong basic conditions required for derivatization. In both humans and rats, the pharmacokinetics of racemic KT were stereoselective with the R enantiomer being predominant (AUC S/R: humans, 0.26; Rats: 0.45). This is likely due to more extensive plasma protein binding of S than its antipode (unbound S/R: 1.35). The discrepancies in the literature may be explaine...Continue Reading

Citations

Sep 1, 2006·Biopharmaceutics & Drug Disposition·Dion R Brocks
Apr 29, 1998·Clinical Pharmacology and Therapeutics·K ParkL B Sheiner
Mar 30, 2007·Chirality·Imran AliBhavtosh Sharma
Jan 1, 1997·Chirality·F JamaliG Aberg
Jan 29, 2002·Anesthesia and Analgesia·Richard M DsidaMichael J Avram
Oct 4, 2011·Anesthesia and Analgesia·Gildasio S De OliveiraHonorio T Benzon
Jun 14, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yuna GuoLaurie G Hudson
Oct 7, 2000·Journal of Pharmaceutical and Biomedical Analysis·F LagrangeB Bannwarth
Apr 11, 1997·Journal of Chromatography. B, Biomedical Sciences and Applications·N M Davies

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