The pharmacokinetics of ketorolac enantiomers following intramuscular administration of the racemate.

A single dose of racemic ketorolac (30 mg of tromethamine salt, Toradol) was administered by bolus intramuscular injection to four young, healthy volunteers. The concentrations of total (bound plus unbound) (R)- and (S)-ketorolac were measured in plasma for 9 h after dosing. The mean +/- s.d. clearance of (S)-ketorolac (45.9 +/- 10.1 ml h-1 kg-1) exceeded (P = 0.0032) that of the (R)-enantiomer (19.0 +/- 5.0 ml h-1 kg-1). The mean +/- s.d. AUC ratio for (S)-ketorolac:(R)-ketorolac (0.442 +/- 0.043) was significantly different from unity (P = 0.0001). The steady-state volume of distribution of (S)-ketorolac (0.135 +/- 0.022 l kg-1) was significantly different (P = 0.0013) from that of its optical antipode (0.075 +/- 0.014 l kg-1) and the half-lives of (S)- and (R)-ketorolac (2.35 +/- 0.23 h and 3.62 +/- 0.79 h, respectively) were also significantly different (P = 0.026). These data indicate that the disposition of ketorolac in man is subject to marked enantioselectivity and, because of possible differences in biological activity of (S)- and (R)-ketorolac, emphasize the need to monitor separate stereoisomer concentrations of the drug if pharmacological data are to be interpreted correctly.

Stereoselective analysis of ketorolac in human plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) analytical method is described for the quantification of the (R)- and (S)-enantiomers of ketorolac when present together in human plasma. The method involves derivatization with thionyl chloride/(S)-1-phenylethylamine and subsequent reversed-phase chromatography of the diastereomeric (S)-1-phenylethylamides of (R)- and (S)-ketorolac. The method is suitable for the analysis of large numbers of plasma samples and has been applied in this report to a pharmacokinetic study of ketorolac enantiomers upon intramuscular administration of racemic drug to a human subject. The limit of quantification for each enantiomer of ketorolac is 50 ng/ml (signal-to-noise ratio > 10).