A single dose of racemic ketorolac (30 mg of the 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-') 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 signifcantly different from unity (P = 0.0001). The steady-state volume of distribution of (S)-ketorolac (0.135 ± 0.0221 kg-1) was significantly different (P = 0.0013) from that of its optical antipode (0.075 ± 0.014 1 kg-') 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.

1 The pharmacokinetics following long term intravenous infusion of lignocaine to cardiac patients have been examined. 2 Plasma levels and half‐lives of lignocaine and monoethylglycinexylidide (MEGX) showed wide inter‐patient variability. 3 Toxicity reactions to therapy were associated with elevated lignocaine and/or MEGX plasma levels. 4 In a separate study the effect of age on the pharmacokinetics of lignocaine was examined using bolus doses (50 mg) of the drug to young and aged subjects. 5 Elderly subjects had significantly longer half‐lives for lignocaine compared to younger individuals although no change in plasma clearance occurred. 6 The drug appeared to distribute differently in the aged as reflected by significantly increased apparent volumes of distribution. 7 The 24 h urinary recovery of the major metabolite (total 4‐hydroxyxylidine) showed a significant reduction in the elderly when compared to the young. 8 The clinical significance of these studies with respect to lignocaine therapy has been discussed.

1 The binding of bupivacaine (400 ng/ml) to isolated al-acid glycoprotein was studied at two protein concentrations. At 20 mg/10O ml the extent of bupivacaine binding was 31.0 ± 1.8% (mean + s.d., n = 4), and at a protein concentration of 60 mg/100 ml binding of bupivacaine was 85.8 + 1.5% (n = 4).2 Bupivacaine and a,-acid glycoprotein concentrations were measured in plasma samples collected from a maternal peripheral vein and the umbilical vein at delivery (n = 23). The ratio of the foetal:maternal bupivacaine concentrations ranged from 0.17 to 0.52, while the foetal:matemal ratio for al-acid glycoprotein concentrations ranged from 0.20 to 0.96. A positive relationship emerged between the two ratios (P < 0.01).3 The al-acid glycoprotein concentration gradient across the placenta, and interindividual variability in the gradient appear to contribute to the low and variable transplacental bupivacaine concentration ratio observed.

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