Comparative disposition of pethidine and norpethidine in old and young patients

Pethidine was given as a single intravenous dose for premedication before minor surgery. Two groups of subjects were studied, old patients aged more than 65 years, and young patients aged 18-30 years. Blood samples were taken at fixed intervals for 30 h after the injection, and the plasma concentrations of pethidine and its major metabolite norpethidine were analyzed by gas chromatography. In comparison with the young the old patients had a lower plasma clearance for pethidine (9.13 +/- 2.50 versus 16.18 +/- 5.15 ml/min/kg), slower elimination rate beta (0.101 +/- 0.036 versus 0.211 +/- 0.146), and a larger AUC (1935 +/- 554 versus 1092 +/- 277 h . ng/ml) but a similar volume of distribution (5.69 +/- 1.54 versus 5.38 +/- 1.75 l/kg). Norpethidine appeared later and reached its peak concentration later in the old patients than in the young. In several old patients it was still present at a plateau level after 30 h. The present study emphasizes that both parent drug and active metabolite must be taken into consideration when drug therapy is evaluated. The data do not provide pharmacokinetic support for a reduction in the dose of pethidine if it is given as a single intravenous dose. However, when repeatedly administered, it is advisable to reduce the total daily dose.