Drug interaction: meperidine and chlorpromazine, a toxic combination.
To determine the effect of chlorpromazine on the serum concentration-time curve and metabolism of meperidine, 10 healthy volunteers were injected on two separate days in a two-way crossover design with 26 mg/m2 meperidine hydrochloride combined with either 30 mg/m2 chlorpromazine or a placebo. The subjects demonstrated the same serum meperidine concentration-time curves after meperidine plus placebo and meperidine plus chlorpromazine. The excretion of the metabolites normeperidine and normeperidinic acid, however, showed a significant increase with the meperidine-chlorpromazine combination. A marked lethargy was observed after the administration of the meperidine-chlorpromazine combinations in most subjects, which was quite debilitating and may have resulted from the alteration of meperidine metabolism by chlorpromazine. The meperidine-chlorpromazine combination also caused a greater mean depression of the systolic and diastolic pressures than the meperidine-placebo combination. The differences in the blood pressure and symptomatology were significant and represent a potential toxicity that may result from the use of the chlorpromazine-meperidine combination.
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002746:Chlorpromazine / Q000008:administration & dosage / Q000009:adverse effects*; D004347:Drug Interactions; D006801:Humans; D008614:Meperidine / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D008657:Metabolic Clearance Rate / Q000187:drug effects
D008614:Meperidine; D002746:Chlorpromazine