Pharmacokinetics of high-dose meperidine in surgical patients

Intravenous meperidine is used during surgical procedures at doses up to 5 mg/kg. At the commonly used analgesic intravenous doses of 50 to 100 mg (0.7 to 1.4 mg/kg), the drug exhibits two-compartment open model pharmacokinetics, with elimination primarily by hepatic metabolism (>90% of a dose). Drugs eliminated to a large extent by metabolism may, however, be subject to dose-dependent kinetics. We therefore studied the pharmacokinetics of meperidine when administered as 5 mg/kg IV bolus injections in surgical patients undergoing corrective vascular surgery involving the lower part of the abdominal aorta and the femoral and popliteal arteries. Serial blood samples were collected over 10 hours and plasma meperidine concentrations were determined by a gas chromatographic assay. Semilogarithmic plots of plasma meperidine concentration vs time were biphasic; however, the curves' irregularities during the time the arterial vessels were clamped suggest that the data should be analyzed in a model-independent manner. These irregularities suggest that the disposition of meperidine is altered during the clamping period and that these alterations are quickly reversed following removal of the clamp. Our findings agree with those reported in the literature following a total dose of 50 mg (half-life average 4.4 hours, total plasma clearance 10.4 ml/min/kg, and apparent volume of distribution 3.74 L/kg). The present results thus indicate that although meperidine is eliminated to a large extent by metabolism, the processes involved are apparently not saturated at doses 7 times greater than normal.