Drug Interaction: Meperidine and Chlorpromazine, a Toxic Combination

Abstract

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 meperdine—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.