No abstract

Pethidine is commonly used in single doses as a preoperative medication or in multiple doses as an analgesic. The clinical consequences of altered disposition are more likely to result from its analgesic use. Correlations between plasma pethidine concentration, analgesia and side effects such as respiratory depression, have been established, but considerable overlap exists between concentrations producing therapeutic and non-therapeutic effects. The current practice of intermittent pethidine administration (intravenous, intramuscular and oral) for analgesia results in fluctuations in pethidine plasma concentrations which are associated with incomplete pain relief and side effects. Continuous intravenous infusion of pethidine may avoid these difficulties. Changes in pethidine disposition have been observed in patients with liver disease and in the elderly. Measurement of plasma pethidine concentrations may be helpful as an aid to the management of such patients. In renal disease, metabolites may accumulate and cause side effects.

1 The disposition of total and free prednisolone has been studied in four male and four female volunteers, each of whom received an intravenous dose of 0.075 mg/kg (low) and 1.5 mg/kg (high) of prednisolone at both 06.00 h and 18.00 h. 2 For the low dose, free prednisolone clearance was 14% lower (P = 0.012) and time-averaged prednisolone free fraction was 22% higher (P < 0.001) in the morning, there being no circadian difference in total prednisolone clearance. There was no circadian differences in prednisolone disposition at the high dose. These findings are consistent with a mechanism in which cortisol causes a simultaneous competitive inhibition of prednisolone clearance and plasma protein binding at low, but not at high prednisolone doses. 3 Prednisolone clearance was higher in female than in male subjects, the mean increase being 18% (P = 0.022) for total prednisolone and 21% (P = 0.036) for free prednisolone. 4 Mean total prednisolone clearance and steady-state distribution volume were two-fold higher at the high vs the low dose (P < 0.001), but free prednisolone clearance showed a dose dependent decrease of 11% (P = 0.019). There was no change in free prednisolone steady-state distribution volume.