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

Details

• Alternative Title:
  Malar J
• Personal Author:
  Green, Michael ; Otieno, Kephas ; Katana, Abraham ; Slutsker, Laurence ; Kariuki, Simon ; Ouma, Peter ; González, Raquel ; Menendez, Clara ; ter Kuile, Feiko ; Desai, Meghna
• Description:
  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.
  
  
• Subjects:
  Adolescent Adult Antimalarials Double-Blind Method Female HIV Infections Humans Malaria Male Mefloquine Pregnancy Pregnancy Complications, Infectious Pregnancy Complications, Parasitic Sulfamethoxazole Trimethoprim Trimethoprim, Sulfamethoxazole Drug Combination Young Adult

  More +
• Source:
  Malar J. 15.
• Pubmed ID:
  26732683
• Pubmed Central ID:
  PMC4700759
• Document Type:
  Journal Article
• Place as Subject:
  Kenya
• Volume:
  15
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:b0c4badd83e2cb0a653800c8be6e76afd6374e4eda3e04bd7ed7cc5e3279ac49
• Download URL:
  https://stacks.cdc.gov/view/cdc/37732/cdc_37732_DS1.pdf
• File Type:
  [PDF - 1.04 MB ]