Population Pharmacokinetics of Antimalarial Naphthoquine in Combination with Artemisinin in Tanzanian Children and Adults: Dose Optimization
| العنوان: | Population Pharmacokinetics of Antimalarial Naphthoquine in Combination with Artemisinin in Tanzanian Children and Adults: Dose Optimization |
|---|---|
| المؤلفون: | Ali Mohamed Ali, Kamunkhwala Gausi, Said A. Jongo, Kamaka R. Kassim, Catherine Mkindi, Beatus Simon, Ali T. Mtoro, Omar A. Juma, Omar N. Lweno, Conrad H. Gwandu, Bakari M. Bakari, Thabiti A. Mbaga, Florence A. Milando, Ali Hamad, Seif A. Shekalaghe, Salim Abdulla, Paolo Denti, Melissa A. Penny |
| المصدر: | Antimicrobial Agents and Chemotherapy. 66 |
| بيانات النشر: | American Society for Microbiology, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Adult, Pharmacology, Adolescent, Body Weight, Tanzania, Artemisinins, Antimalarials, 1-Naphthylamine, Infectious Diseases, parasitic diseases, Aminoquinolines, Folic Acid Antagonists, Humans, Pharmacology (medical), Malaria, Falciparum, Child, Naphthoquinones |
| الوصف: | The combination antimalarial therapy of artemisinin-naphthoquine (ART-NQ) was developed as a single-dose therapy, aiming to improve adherence relative to the multiday schedules of other artemisinin combination therapies. The pharmacokinetics of ART-NQ has not been well characterized, especially in children. A pharmacokinetic study was conducted in adults and children over 5 years of age (6 to 10, 11 to 17, and >/=18 years of age) with uncomplicated malaria in Tanzania. The median weights for the three age groups were 20, 37.5, and 55 kg, respectively. Twenty-nine patients received single doses of 20 mg/kg of body weight for artemisinin and 8 mg/kg for naphthoquine, and plasma drug concentrations were assessed at 13 time points over 42 days from treatment. We used nonlinear mixed-effects modeling to interpret the data, and allometric scaling was employed to adjust for the effect of body size. The pharmacokinetics of artemisinin was best described by one-compartment model and that of naphthoquine by a two-compartment disposition model. Clearance values for a typical patient (55-kg body weight and 44.3-kg fat-free mass) were estimated as 66.7 L/h (95% confidence interval [CI], 57.3 to 78.5 L/h) for artemisinin and 44.2 L/h (95% CI, 37.9 to 50.6 L/h) for naphthoquine. Nevertheless, we show via simulation that patients weighing >/=70 kg achieve on average a 30% lower day 7 concentration compared to a 48-kg reference patient at the doses tested, suggesting dose increases may be warranted to ensure adequate exposure. (This study has been registered at ClinicalTrials.gov under identifier NCT01930331.). |
| وصف الملف: | application/pdf |
| تدمد: | 1098-6596 0066-4804 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::238c524f12b9874fc218c35ccc697859 https://doi.org/10.1128/aac.01696-21 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....238c524f12b9874fc218c35ccc697859 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10986596 00664804 |
|---|