5 years ago

Suboptimal Cotrimoxazole prophylactic concentrations in HIV-infected children according to the WHO guidelines

, M. Amorissani-Folquet, C. Pressiat, F. Eboua, V. Mea-Assande, D. Hirt, V. Leroy, Y. Zheng, D.-L. Dahourou, K. Malateste, D. Ye, S. Blanche, J.-M. Treluyer, G. Lui, C. Yonaba
Aims A clinical study was conduct in HIV-infected children to evaluate the prophylactic doses of cotrimoxazole (sulfamethoxazole (SMX) and trimethoprim (TMP)) advised by WHO. Methods Children received lopinavir-based antiretroviral therapy with cotrimoxazole prophylaxis (200 mg of SMX/ 40 mg of TMP once daily). Nonlinear mixed effects modelling approach was used to analyze plasma concentrations. Factors that could impact the pharmacokinetic profile were investigate. The model was subsequently used to simulate individual exposure and evaluate different administration schemes. Results The cohort counted 136 children (average age: 1.9 years (range: [0.7-4]), average weight: 9.5 kg (range: [6-16.3]). A dose per kg was justified by the significant influence of implementing an allometrically scaled body size covariate on SMX and TMP pharmacokinetic. SMX and TPM clearance were estimated at 0.49 L/h/9.5 kg and 3.06 L/h/9.5 kg respectively. The simulated exposures obtained after administration of oral dosing recommended by WHO for children from 10 to 15 kg were significantly lower than in adult for SMX and TMP. This could induce a reduction of effectiveness of cotrimoxazole. Simulations show that regimens of 30 mg/kg of SMX and 6 mg/kg of TMP in the group of 5 to 10 kg and 25 mg/kg of SMX and 5mg/kg of TMP in the group of 10 to 15 are more pertinent doses Conclusions In this context of high prevalence of opportunistic infections, a lower exposure to cotrimoxazole in children than adults was noted. To achieve comparable exposure to adult a dosing scheme per kg was proposed.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/bcp.13397

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.