دورية أكاديمية
Understanding Drug Exposure and Trichuris trichiura Cure Rates: A Pharmacometric Approach for Albendazole-Ivermectin Co-medication in Tanzania and Côte d'Ivoire.
| العنوان: | Understanding Drug Exposure and Trichuris trichiura Cure Rates: A Pharmacometric Approach for Albendazole-Ivermectin Co-medication in Tanzania and Côte d'Ivoire. |
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| المؤلفون: | Pillay-Fuentes Lorente V; Division of Clinical Pharmacology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; APT-Africa Fellowship Program, c/o Pharmacometrics Africa NPC, Groote Schuur Hospital, Cape Town, South Africa., Nwogu-Attah JN; APT-Africa Fellowship Program, c/o Pharmacometrics Africa NPC, Groote Schuur Hospital, Cape Town, South Africa. nwogu.jacinta@lcu.edu.ng.; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Lead City University, Off Oba Otudeko Avenue, Toll-Gate Area, Ibadan, 200255, Oyo, Nigeria. nwogu.jacinta@lcu.edu.ng., Steffens B; Pediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital (UKBB), Basel, Switzerland., Bräm D; Pediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital (UKBB), Basel, Switzerland., Sprecher V; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Allschwil Switzerland, University of Basel, Basel, Switzerland.; Paediatric Infectious Diseases, Children's Hospital of Central Switzerland (KidZ), Lucerne Cantonal Hospital, Lucerne, Switzerland., Hofmann D; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Allschwil Switzerland, University of Basel, Basel, Switzerland., Buettcher M; Pediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital (UKBB), Basel, Switzerland.; Paediatric Infectious Diseases, Children's Hospital of Central Switzerland (KidZ), Lucerne Cantonal Hospital, Lucerne, Switzerland.; Faculty of Health Sciences and Medicine, University Lucerne, Lucerne, Switzerland., Pillai G; APT-Africa Fellowship Program, c/o Pharmacometrics Africa NPC, Groote Schuur Hospital, Cape Town, South Africa.; Division of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa.; CP+ Associates GmbH, Basel, Switzerland., Mouksassi S; Certara Inc., Princeton, NJ, USA., Coulibaly J; Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, Abidjan, Ivory Coast.; Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, Abidjan, Ivory Coast., Pfister M; Pediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital (UKBB), Basel, Switzerland., Keiser J; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Allschwil Switzerland, University of Basel, Basel, Switzerland.; Paediatric Infectious Diseases, Children's Hospital of Central Switzerland (KidZ), Lucerne Cantonal Hospital, Lucerne, Switzerland. |
| المصدر: | Drugs in R&D [Drugs R D] 2024 Jun; Vol. 24 (2), pp. 331-340. Date of Electronic Publication: 2024 Jul 22. |
| نوع المنشور: | Journal Article; Randomized Controlled Trial |
| اللغة: | English |
| بيانات الدورية: | Publisher: Adis, Springer International Country of Publication: New Zealand NLM ID: 100883647 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1179-6901 (Electronic) Linking ISSN: 11745886 NLM ISO Abbreviation: Drugs R D Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Auckland : Adis, Springer International Original Publication: Auckland ; Philadelphia : Adis International, c1999- |
| مواضيع طبية MeSH: | Albendazole*/pharmacokinetics , Albendazole*/analogs & derivatives , Albendazole*/administration & dosage , Albendazole*/pharmacology , Albendazole*/therapeutic use , Trichuris*/drug effects , Trichuriasis*/drug therapy , Ivermectin*/pharmacokinetics , Ivermectin*/therapeutic use , Ivermectin*/pharmacology , Ivermectin*/analogs & derivatives , Drug Therapy, Combination*, Humans ; Cote d'Ivoire ; Adolescent ; Tanzania ; Child ; Young Adult ; Male ; Female ; Animals ; Anthelmintics/pharmacokinetics ; Anthelmintics/therapeutic use ; Anthelmintics/administration & dosage |
| مستخلص: | Background and Objective: Trichuriasis caused by the human whipworm Trichuris trichiura poses a significant public health concern. Albendazole-ivermectin co-medication is currently the most effective treatment. Studies conducted in Tanzania and Côte d'Ivoire unveiled differences in efficacy for albendazole-ivermectin combination therapy in both countries. A pharmacometrics approach was used to assess co-medication and study population effects on the pharmacokinetics of the two main metabolites of albendazole. An exploratory exposure-efficacy analysis was also carried out to investigate relationships between exposure measures and the egg reduction rate. Methods: Pharmacokinetic data from studies in Tanzania and Côte d'Ivoire in adolescents (aged 12-19 years) were included in the pharmacometric analysis. Participants received a single dose of either albendazole 400 mg alone or in combination with ivermectin 200 µg/kg. A pharmacometric analysis was performed to investigate the potential effects of the study population and co-administered ivermectin on the apparent clearance of the metabolites of albendazole. Non-linear mixed-effects modeling was conducted with MonolixSuite 2023R1. The pharmacokinetic exposure measures derived from simulations with individual model parameters were used in the exploratory-exposure response analysis. Results: Pharmacokinetic profiles were best described by a two-compartment model for albendazole sulfoxide and a one-compartment model for albendazole sulfone, with a transit compartment and linear elimination. While no co-medication effect was found, apparent clearance of albendazole sulfoxide (albendazole sulfone) in the Tanzanian study population was 75% (46%) higher than that in the Côte d'Ivoire study population. Exposure-efficacy response analyses indicated that peak concentration and the time-above-exposure threshold were associated with the egg reduction rate. Conclusions: Study population but not co-administered ivermectin showed an effect on apparent clearance of albendazole sulfoxide and albendazole sulfone. Polymorphisms in drug-metabolizing enzymes and host-parasite interaction may explain this result. Difference in drug exposure did not explain the disparate efficacy responses in Tanzania and Côte d'Ivoire. Peak concentration and time-above-threshold were exposure measures associated with the egg reduction rate. Further studies evaluating genetic and resistance patterns in various regions in Africa are warranted. (© 2024. The Author(s).) |
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| معلومات مُعتمدة: | OPP1153928 Bill and Melinda Gates Foundation |
| المشرفين على المادة: | F4216019LN (Albendazole) 70288-86-7 (Ivermectin) 0 (Anthelmintics) |
| تواريخ الأحداث: | Date Created: 20240721 Date Completed: 20240809 Latest Revision: 20240812 |
| رمز التحديث: | 20240813 |
| مُعرف محوري في PubMed: | PMC11315861 |
| DOI: | 10.1007/s40268-024-00476-4 |
| PMID: | 39034337 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1179-6901 |
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| DOI: | 10.1007/s40268-024-00476-4 |