THE PHARMACOKINETICS OF KETOROLAC ENANTIOMERS FOLLOWING INTRAMUSCULAR ADMINISTRATION OF THE RACEMATE

A single dose of racemic ketorolac (30 mg of the tromethamine salt, Toradol(R)) 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.