Pethidine pharmacokinetics after intramuscular dose: a comparison in Caucasian, Chinese and Nepalese patients

The pharmacokinetics of pethidine after a single intramuscular injection were studied in 30 male patients of Caucasian, Chinese and Nepalese extraction. There were no significant differences between the three ethnic groups in the mean time for maximum absorption (tmax) and peak plasma concentration (Cmax) of pethidine. The mean (+/- S.D.) elimination half life (t1/2) of pethidine was shorter in Caucasians (4.5 +/- 1.3 h) compared with Nepalese (6.3 +/- 1.6 h) and Chinese (8.1 +/- 3.1 h) (p < 0.01). The plasma clearance of pethidine was greater in Caucasians (14.2 +/- 4.8 ml.min-1.kg-1) than in Nepalese (12.6 +/- 2.9 ml.min-1.kg-1) and Chinese (10.0 +/- 2.9 ml.min-1.kg-1) (p < 0.05); yet the apparent renal clearance was similar (64.1 +/- 22.9, 86.7 +/- 44.5 and 61.4 +/- 30.1 ml.min-1.kg-1, respectively, for the Chinese (n = 6), Caucasian (n = 6) and Nepalese (n = 9) patients). No apparent ethnic differences were found in the tmax and Cmax of norpethidine which emerged as the major metabolite in the plasma in the three races. An apparently higher area under plasma concentration-time curve (AUC infinity [symbol: see text]) and longer elimination t1/2 of the metabolite were observed in the two Asian patient groups. It appears that both the Chinese and Indian groups did not eliminate pethidine as effectively as the Caucasians after a single intramuscular injection, which may be the result of interethnic variability in the metabolism of pethidine. Caution may be required on multiple dosing of pethidine in Asian patients due to the possible accumulation of the parent drug and its toxic metabolite, norpethidine.