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  • Title: Effect of oral contraceptive steroids on the clinical course of malaria infection and on the pharmacokinetics of mefloquine in Thai women.
    Author: Karbwang J, Looareesuwan S, Back DJ, Migasana S, Bunnag D, Breckenridge AM.
    Journal: Bull World Health Organ; 1988; 66(6):763-7. PubMed ID: 3266115.
    Abstract:
    6 healthy Thai women volunteers who regularly used oral contraceptives (OCs) and 12 Thai women patients with falciparum malaria, 6 of whom also were using OCs, participated in this study designed to evaluate the results of an investigation of the pharmacokinetics of mefloquine, an effective treatment for multidrug-resistant malaria, and the clinical course of malaria infection in OC users. The healthy volunteers received 3 tablets of mefloquine, each containing 250 mg mefloquine base and 1 tablet daily of a combined OC containing 0.5 mg norgestrel and 0.05 mg ethinylestradiol. Group 1 patients (non-OC users with falciparum malaria) received 3 tablets of mefloquine; group 2 patients (OC users with falciparum malaria) received 3 tablets of mefloquine plus 1 tablet daily of the OC. The level of mefloquine was determined by high-performance liquid chromatography. The area under the plasma mefloquine concentration-time curve (AUC) was determined using the trapezoidal rule. The 6 healthy volunteers who used OCs tolerated 750 mg mefloquine well. The main side effects were transient nausea and vomiting (3 subjects) that required no treatment. All patients with malaria infection had a history of fever that lasted 1-3 days and all but 1 was febrile. The geometric mean of the parasite counts was greater and the mean erythrocyte volume fraction was higher among non-OC users. There was no statistically significant differences between OC users and nonusers in exhibited fever and parasite clearance times. There was considerable interindividual variation in the peak plasma concentration of mefloquine, particularly among the OC users. No significant differences were found between the pharmacokinetic parameters for the OC users and nonOC users. There were significant differences between the parameters for the OC user volunteers and those for the OC user patients: the healthy volunteers had a significantly longer and mean retention time than patients. The study findings fail to indicate that OCs had any major deleterious effect on the course of human falciparum malaria.
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