Abstract: | The pharmacokinetics of intravenous pethidine (150 micrograms kg-1) were determined in 10 healthy Chinese subjects under controlled (acidic and alkaline) and uncontrolled urinary pH. Large variations in the 48 hr urinary recoveries of pethidine and norpethidine were induced by change in urinary pH: (mean +/- S.D.): 24.3 +/- 7.3% & 33.0 +/- 11.4%, 0.4 +/- 0.3% & 3.8 +/- 2.2%, 11.4 +/- 6.9% & 13.9 +/- 2.5%, respectively, under acidic, alkaline and uncontrolled urinary pH for pethidine and norpethidine. There was no significant difference in the terminal half-lives, t 1/2 (6.1 to 7.0 hr) of pethidine, although the area under the plasma concentration-time curve under acidic urinary conditions was slightly lower and renal clearance of the drug higher than those under alkaline and uncontrolled urinary conditions. Confirming previous results from Caucasian subjects, under all 3 conditions pethidine disappeared from the plasma tri-exponentially and acidification of the urine may increase body clearance of unchanged pethidine due mainly to greater renal clearance of the drug; this may be useful clinically to treat acute pethidine poisoning. However, under acidic urinary conditions, Chinese subjects excreted more norpethidine than Caucasians (33.0 +/- 11.4% and 23.4 +/- 4.6%, respectively). |