Disposition of pethidine in man under acidic urinary pH. 3. A comparison of pharmacokinetics among Caucasian, Chinese and Indian subjects

Abstract

The pharmacokinetics of low dose pethidine (150 micrograms kg-1) after intravenous administration were determined in 10 Caucasian, 10 Chinese and 10 Indian healthy volunteers under conditions of acidic urinary pH. Plasma and urine concentrations of pethidine and norpethidine were measured by gas liquid chromatography. In all 3 ethnic groups, the disappearance of pethidine from plasma was best described by a tri-exponential function. No significant differences were observed in the elimination half life, renal clearance and total plasma clearance of the drug. The significantly lower AUC and higher (approaching significance) apparent volume of distribution in the 2 Asian groups may be explained in terms of more readily distribution of the drug (significantly higher K21 rate constants were obtained from both Chinese and Indian subjects according to a 3-compartment open model) due possibly to more frequent movement of these subjects during the early part of experiment. More norpethidine was recovered in the urine of the Chinese and Indian subjects; this may suggest an interethnic difference in the oxidative demethylation of pethidine.