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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-infected women in Kenya..

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Desai, Meghna, Green, Michael, González, Raquel, Kariuki, Simon, Katana, Abraham, Menendez,, Clara, Ouma, Peter, Kephas, Otieno, Slutsker, Laurence and terKuile, Feiko ORCID: https://orcid.org/0000-0003-3663-5617 (2016) 'Pharmacokinetics of mefloquine and its effect on sulfamethoxazole and trimethoprim steady-state blood levels in intermittent preventive treatment (IPTp) of pregnant HIV-infected women in Kenya..'. Malaria Journal, Vol 15, Issue 7.

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Abstract

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.

Item Type: Article
Additional Information: Open access >SM Subjects >SM
Subjects: WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WQ Obstetrics > Pregnancy Complications > WQ 256 Infectious diseases
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1186/s12936-015-1049-9
Depositing User: Stacy Murtagh
Date Deposited: 23 Feb 2016 14:55
Last Modified: 06 Feb 2018 13:11
URI: http://archive.lstmed.ac.uk/id/eprint/5693

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