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Pharmacokinetics of mefloquine and its effect on sulfamethoxazole and trimethoprim steady-state blood levels in intermittent preventive treatment (IPTp) of pregnant HIV …

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dc.contributor.author Michael Green, Kephas Otieno, Abraham Katana, Laurence Slutsker, Simon Kariuki, Peter Ouma, Raquel González, Clara Menendez, Feiko ter Kuile, Meghna Desai
dc.date.accessioned 2021-01-08T09:42:14Z
dc.date.available 2021-01-08T09:42:14Z
dc.date.issued 2016
dc.identifier.uri https://repository.maseno.ac.ke/handle/123456789/3509
dc.description.abstract Background 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. Methods A 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. Results Sulfamethoxazole/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. Conclusions Although 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. en_US
dc.publisher BioMed Central en_US
dc.title Pharmacokinetics of mefloquine and its effect on sulfamethoxazole and trimethoprim steady-state blood levels in intermittent preventive treatment (IPTp) of pregnant HIV … en_US
dc.type Article en_US


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