Disposition of pethidine in man under acidic urinary PH. I. Plasma level and urinary elimination of pethidine and norpethidine.

A detailed study on the plasma and urine levels of pethidine and its major basic metabolite, norpethidine, was carried out after intravenous and oral administration of pethidine, under conditions of controlled acidic urinary pH, to two healthy subjects who had previously shown significant difference in the urinary recovery of pethidine after the intramuscular administration of a standard dose. Utilizing the data of area under plasma concentration-time curve and cumulative urinary excretion of pethidine, similar values of renal clearance of the drug were obtained after separate intravenous and oral administration to the same subject. There is an overall difference in the renal clearance and metabolic pattern of the drug between these two subjects under conditions of controlled acidic urinary pH. It is postulated that variation in the overall elimination of pethidine and other weakly basic drugs can only be elucidated under conditions and may be interpreted in terms of differences in the renal clearance and hepatic biotransformation of the drug.