Drug Interactions I: Meperidine and Combination Oral Contraceptives

Abstract

Meperidine is a widely-used narcotic analgesic. Alteration of the hepatic metabolism of the drug has been reported as a result of other drug interactions. One report involving meperidine and combination-type oral contraceptives found a greater excretion of meperidine versus normeperidine in those using contraceptive hormones suggesting that these drugs inhibit the N-demethylation of meperidine. This paper reports results of a study of this interaction. Group 1 consisted of 8 normal men; Group 2 8 normal women who had not taken any oral contraceptive for at least a year; Group 3 8 normal women taking Ovral containing .5 mg norgestrel and .05 mg ethinyl estradiol. On Day 1 of the study all subjects were given an intramuscular injection of 50 mg meperidine hydrochloride. Plasma samples were collected at 0 1/2 1 2 4 6 8 and 24 hours after the injection. A cumulative urinary output was collected at each sampling time and at 48 hours. The study was repeated after at least a week. Details of analysis technique are given. Mean serum levels for all groups reached maximum at 1 hour with complete plasma clearance at 24 hours. No significant differences between the serum levels of the 3 groups at any sampling time were found. Meperidine was detected in the urine at 1 hour after injection. No significant difference in the urinary excretion of the 3 groups was found. No significant differences among the cumulative excretions of normeperidine were noted. The metabolism of meperidine is apparently not affected by this oral contraceptive. These results conflict with some previously reported findings by others. The earlier reports are considered to have been in error.