Population Pharmacokinetics of the Antimalarial Amodiaquine: a Pooled Analysis To Optimize Dosing
| العنوان: | Population Pharmacokinetics of the Antimalarial Amodiaquine: a Pooled Analysis To Optimize Dosing |
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| المؤلفون: | Ali, Ali Mohamed, Penny, Melissa, Smith, Thomas, Workman, Lesley, Sasi, Philip, Adjei, George O, Aweeka, Francesca, Kiechel, Jean-René, Jullien, Vincent, Rijken, Marcus, Mcgready, Rose, Mwesigwa, Julia, Kristensen, Kim, Stepniewska, Kasia, Tarning, Joel, Barnes, Karen, Denti, Paolo, Massougbodji, Achille, Gansané, Adama, Adeothy, Adicat, Aubouy, Agnès, Ouedraogo, Alphonse, Annerberg, Anna, Bruneel, Arnaud, Phyo, Aung Pyae, Win, Aye Kyi, Benakis, A., Goka, Bamenla, Gourmel, Bernard, Ogutu, Bernhards, Schramm, Birgit, McGee, Bryan, Morgan, Caroline, Obonyo, Charles, Mazinda, Charles, Parzy, D., Ashley, Elizabeth, Baudin, Elisabeth, Juma, Elizabeth, Comte, Eric, Ouedraogo, Esperance, Nosten, François, Sugnaux, F., Cottrell, Gilles, Dorsey, Grant, Carn, Gwenaelle, Kossou, Hortense, Amedome, Hyacinthe, Kalyango, Joan, Faucher, Jean-François, Jones, Joel, Simpson, Julie, Doritchamou, Justin, Kurtzhals, J., Pinoges, Loretxu, Hoegberg, Lotte, BERTAUX, L., Malaika, L. Tshilolo Muepu, Bergstrand, Martin, Alifrangis, Michael, Branger, Michel, Cot, Michel, Cammas, Mireille, Kamya, Moses, Day, Nicholas, White, Nicholas, Taudon, N., Rodrigues, Onike, Chotsiri, Palang, Valeh, Parastou, Houzé, Pascal, Deloron, Philippe, Guérin, Philippe, Rosenthal, Philip, Hsi, Poe, German, Polina, Singhasivanon, Pratap, Smith, Richard, Lwango, R., Sirima, Sodiomon, Parikh, Sunil, Alegre, S. Sese, Clark, Tamara, Sundaygar, Timothy, Drysdale, Troy, Taylor, Walter, Sinou, V., Zolia, Yah |
| المساهمون: | Swiss Tropical and Public Health Institute [Basel], University of Basel (Unibas), Ifakara Health Institute, University of Cape Town, Muhimbili University of Health and Allied Sciences, University of Ghana, University of California, Drugs for Neglected Diseases Initiative, Service de Pharmacologie, Hôpital Européen George Pompidou, Université Paris Descartes, Paris, France, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Mahidol University [Bangkok], University of Oxford [Oxford], London School of Hygiene & Tropical Medicine [Fajara, The Gambia], University of Antwerp (UA), Development DMPK-PKPD, Novo Nordisk, Copenhagen, Denmark, Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Dis Syst Biol,Ctr Prot Res, Copenhagen, Denmark, Partenaires INRAE-Partenaires INRAE |
| المصدر: | Antimicrobial Agents and Chemotherapy Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2018, 62 (10), pp.e02193-17. ⟨10.1128/AAC.02193-17⟩ |
| بيانات النشر: | HAL CCSD, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | pediatrics, dose optimization, malaria, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, NONMEM |
| الوصف: | International audience; Amodiaquine plus artesunate is the recommended antimalarial treatment in many countries where malaria is endemic. However, pediatric doses are largely based on a linear extrapolation from adult doses. We pooled data from previously published studies on the pharmacokinetics of amodiaquine, to optimize the dose across all age groups. Adults and children with uncomplicated malaria received daily weight-based doses of amodiaquine or artesunate-amodiaquine over 3 days. Plasma concentration-time profiles for both the parent drug and the metabolite were characterized using nonlinear mixed-effects modeling. Amodiaquine pharmacokinetics were adequately described by a two-compartment disposition model, with first-order elimination leading to the formation of desethylamodiaquine, which was best described by a three-compartment disposition model. Body size and age were the main covariates affecting amodiaquine clearance. After adjusting for the effect of weight, clearance rates for amodiaquine and desethylamodiaquine reached 50% of adult maturation at 2.8 months (95% confidence interval [CI], 1.5 to 3.7 months) and 3.9 months (95% CI, 2.6 to 5.3 months) after birth, assuming that the baby was born at term. Bioavailability was 22.4% (95% CI, 15.6 to 31.9%) lower at the start of treatment than during convalescence, which suggests a malaria disease effect. Neither the drug formulation nor the hemoglobin concentration had an effect on any pharmacokinetic parameters. Results from simulations showed that current manufacturer dosing recommendations resulted in low desethylamodiaquine exposure in patients weighing 8 kg, 15 to 17 kg, 33 to 35 kg, and >62 kg compared to that in a typical 50-kg patient. We propose possible optimized dosing regimens to achieve similar drug exposures among all age groups, which require further validation. |
| اللغة: | English |
| تدمد: | 0066-4804 1098-6596 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::3bb3bd18f3fc311c9c6b237e07f75e3eTest https://hal-univ-tlse3.archives-ouvertes.fr/hal-03136362Test |
| رقم الانضمام: | edsair.dedup.wf.001..3bb3bd18f3fc311c9c6b237e07f75e3e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00664804 10986596 |
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