Abstract
BackgroundIntermittent preventive treatment in pregnancy with sulfadoxine/pyrimethamine is contra-indicated in HIV-positive pregnant women receiving sulfamethoxazole/trimethoprim prophylaxis. Since mefloquine is being considered as a replacement for sulfadoxine/pyrimethamine in this vulnerable population, an investigation on the pharmacokinetic interactions of mefloquine, sulfamethoxazole and trimethoprim in pregnant, HIV-infected women was performed.MethodsA double-blinded, placebo-controlled study was conducted with 124 HIV-infected, pregnant women on a standard regimen of sulfamethoxazole/trimethoprim prophylaxis. Seventy-two subjects received three doses of mefloquine (15 mg/kg) at monthly intervals. Dried blood spots were collected from both placebo and mefloquine arms four to 672 h post-administration and on day 7 following a second monthly dose of mefloquine. A novel high-performance liquid chromatographic method was developed to simultaneously measure mefloquine, sulfamethoxazole and trimethoprim from each blood spot. Non-compartmental methods using a naïve-pooled data approach were used to determine mefloquine pharmacokinetic parameters.ResultsSulfamethoxazole/trimethoprim prophylaxis did not noticeably influence mefloquine pharmacokinetics relative to reported values. The mefloquine half-life, observed clearance (CL/f), and area-under-the-curve (AUC0→∞) were 12.0 days, 0.035 l/h/kg and 431 µg-h/ml, respectively. Although trimethoprim steady-state levels were not significantly different between arms, sulfamethoxazole levels showed a significant 53 % decrease after mefloquine administration relative to the placebo group and returning to pre-dose levels at 28 days.ConclusionsAlthough a transient decrease in sulfamethoxazole levels was observed, there was no change in hospital admissions due to secondary bacterial infections, implying that mefloquine may have provided antimicrobial protection.
Highlights
Intermittent preventive treatment in pregnancy with sulfadoxine/pyrimethamine is contra-indicated in human immunodeficiency virus (HIV)-positive pregnant women receiving sulfamethoxazole/trimethoprim prophylaxis
Since physiological functions are altered during pregnancy, the pharmacokinetics of many anti-malarials are different in pregnant women compared to non-pregnant women [3,4,5]
Mefloquine pharmacokinetics the population pharmacokinetics approach can accommodate sparse data and provide information on the impact of covariates, it requires the use of sophisticated software, which may not be available to everyone
Summary
Intermittent preventive treatment in pregnancy with sulfadoxine/pyrimethamine is contra-indicated in HIV-positive pregnant women receiving sulfamethoxazole/trimethoprim prophylaxis. Since mefloquine is being considered as a replacement for sulfadoxine/pyrimethamine in this vulnerable population, an investigation on the pharmacokinetic interactions of mefloquine, sulfamethoxazole and trimethoprim in pregnant, HIV-infected women was performed. Some reports show that malaria increases the incidence of mother-to-child HIV transmission as well as contributing to low birth weight and maternal anaemia [1, 2]. Drugs used to treat HIV and associated infections may cause serious drug interactions. HIV-infected patients receiving co-trimoxazole (sulfamethoxazole/trimethoprim) prophylaxis should not take another sulfonamide-containing drug, such as sulfadoxine/pyrimethamine (SP), as the risk of sulfonamideinduced adverse effects is increased. Since physiological functions are altered during pregnancy, the pharmacokinetics of many anti-malarials are different in pregnant women compared to non-pregnant women [3,4,5]
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