التفاصيل البيبلوغرافية
| العنوان: |
Population Pharmacokinetics of Hydroxychloroquine and 3 Metabolites in COVID-19 Patients and Pharmacokinetic/Pharmacodynamic Application. |
| المؤلفون: |
Alvarez, Jean Claude1 (AUTHOR) isabelle.etting@aphp.fr, Davido, Benjamin2 (AUTHOR) benjamin.davido@aphp.fr, Moine, Pierre3 (AUTHOR) pierre.moine@aphp.fr, Etting, Isabelle1 (AUTHOR) islamamine.larabi@aphp.fr, Annane, Djillali3 (AUTHOR) djillali.annane@aphp.fr, Larabi, Islam Amine1 (AUTHOR), Simon, Nicolas4 (AUTHOR) nicolas.simon@ap-hm.fr |
| المصدر: |
Pharmaceuticals (14248247). Feb2022, Vol. 15 Issue 2, p256. 1p. |
| مصطلحات موضوعية: |
*COVID-19, *HYDROXYCHLOROQUINE, *METABOLITES, *HOSPITAL patients, *VORICONAZOLE, *TREATMENT effectiveness |
| مستخلص: |
We develop a population pharmacokinetic model for hydroxychloroquine (HCQ) and three of its metabolites (desethylhydroxychloroquine, Des HCQ; desethylchloroquine, DesCQ; and didesethylchloroquine, didesCQ) in COVID-19 patients in order to determine whether a pharmacokinetic (PK)/pharmacodynamic (PD) relationship was present. The population PK of HCQ was described using non-linear mixed effects modelling. The duration of hospitalization, the number of deaths, and poor clinical outcomes (death, transfer to ICU, or hospitalization ≥ 10 d) were evaluated as PD parameters. From 100 hospitalized patients (age = 60.7 ± 16 y), 333 BHCQ and M were available for analysis. The data for BHCQ were best described by a four-compartment model with a first-order input (KA) and a first-order output. For M, the better model of the data used one compartment for each metabolite with a first-order input from HCQ and a first-order output. The fraction of HCQ converted to the metabolites was 75%. A significant relationship was observed between the duration of hospitalization and BHCQ at 48 h (r2 = 0.12; p = 0.0052) or 72 h (r2 = 0.16; p = 0.0012). At 48 h or 72 h, 87% or 91% of patients vs. 63% or 62% had a duration < 25 d with a BHCQ higher or below 200 μg/L, respectively. Clinical outcome was significantly related to BHCQ at 48 h (good outcome 369 +/− 181 μg/L vs. poor 285 +/− 144 μg/L; p = 0.0441) but not at 72 h (407 +/− 207 μg/L vs. 311 +/− 174 μg/L; p = 0.0502). The number of deaths was not significantly different according to the trough concentration (p = 0.972 and 0.836 for 48 h and 72 h, respectively). [ABSTRACT FROM AUTHOR] |
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