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Drug interaction: meperidine and chlorpromazine, a toxic combination

Stambaugh JE Jr and IW Wainer

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.
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