Population Pharmacokinetics of Hydroxychloroquine in COVID-19 Patients: Implications for Dose Optimization
| Autor: | Leila Belkhir, Kevin-Alexandre Delongie, Pierre Wallemacq, Veerle Verlinden, Xavier Wittebole, Cecile Lescrainier, Jamila Hamdani, Flora T. Musuamba, Rakan Nasreddine, Martin Vandeputte, Pauline Thémans, Francoise Wuillaume, Julien De Greef, Jean-Michel Dogné, Nicolas Dauby, Jean-Cyr Yombi, Sophie Kiridis |
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| Přispěvatelé: | UCL - SSS/IREC/LTAP - Louvain Centre for Toxicology and Applied Pharmacology, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service de médecine interne générale, UCL - (SLuc) Service de soins intensifs, UCL - (SLuc) Service de biochimie médicale |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Pediatrics medicine.medical_specialty Coronavirus disease 2019 (COVID-19) Pneumonia Viral Population Biological Availability Pharmacologie 030226 pharmacology & pharmacy Antimalarials Young Adult 03 medical and health sciences 0302 clinical medicine Pharmacokinetics medicine Humans Distribution (pharmacology) Pharmacology (medical) Dosing Original Research Article education Pandemics Aged Aged 80 and over Pharmacology education.field_of_study business.industry COVID-19 Hydroxychloroquine Middle Aged COVID-19 Drug Treatment Bioavailability Clinical trial 030220 oncology & carcinogenesis Female Coronavirus Infections business medicine.drug |
| Zdroj: | European Journal of Drug Metabolism and Pharmacokinetics Thémans, P, Belkhir, L, Dauby, N, Yombi, J C, De Greef, J, Delongie, K A, Vandeputte, M, Nasreddine, R, Wittebole, X, Wuillaume, F, Lescrainier, C, Verlinden, V, Kiridis, S, Dogné, J M, Hamdani, J, Wallemacq, P & Musuamba Tshinanu, F 2020, ' Population Pharmacokinetics of Hydroxychloroquine in COVID-19 Patients : Implications for Dose Optimization ', European Journal of Drug Metabolism and Pharmacokinetics, vol. 45, no. 6, pp. 703-713 . https://doi.org/10.1007/s13318-020-00648-y European journal of drug metabolism and pharmacokinetics, Vol. 45, no.6, p. 703-713 (2020) European journal of drug metabolism and pharmacokinetics, 45 (6 |
| ISSN: | 2107-0180 0378-7966 |
| Popis: | Background and Objective: In the absence of characterization on pharmacokinetics and reference concentrations for hydroxychloroquine in COVID-19 patients, the dose and treatment duration for hydrochloroquine are currently empirical, mainly based on in vitro data, and may vary across national guidelines and clinical study protocols. The aim of this paper is to describe the pharmacokinetics of hydroxychloroquine in COVID-19 patients, considered to be a key step toward its dosing optimization. Methods: We have developed a population pharmacokinetic model for hydroxychloroquine in COVID-19 patients using prospectively collected pharmacokinetic data from patients either enrolled in a clinical trial or treated with hydroxychloroquine as part of standard of care in two tertiary Belgian hospitals. Results: The final population pharmacokinetic model was a one-compartment model with first-order absorption and elimination. The estimated parameter values were 9.3/h, 860.8 L, and 15.7 L/h for the absorption rate constant, the central compartment volume, and the clearance, respectively. The bioavailability factor was fixed to 0.74 based on previously published models. Model validations by bootstraps, prediction corrected visual predictive checks, and normalized prediction distribution errors gave satisfactory results. Simulations were performed to compare the exposure obtained with alternative dosing regimens. Conclusion: The developed models provide useful insight for the dosing optimization of hydroxychloroquine in COVID-19 patients. The present results should be used in conjunction with exposure-efficacy and exposure-safety data to inform optimal dosing of hydroxychloroquine in COVID-19. SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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