Population Pharmacokinetics of Intravenous and Oral Acyclovir and Oral Valacyclovir in Pediatric Population To Optimize Dosing Regimens
| Autor: | Coralie Briand, S Winter, M. Bendavid, Zeynep Demir, Carmen Capito, Mehdi Oualha, Naïm Bouazza, Sana Boujaafar, S Abdalla, Sihem Benaboud, Yi Zheng, Frantz Foissac, Agathe Béranger, Déborah Hirt, Inès Gana, J-M Tréluyer |
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| Rok vydání: | 2020 |
| Předmět: |
viruses
Acyclovir Administration Oral Renal function Population pharmacokinetics Pharmacology medicine.disease_cause Antiviral Agents 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Humans Medicine Pharmacology (medical) Dosing Child 0303 health sciences medicine.diagnostic_test 030306 microbiology business.industry virus diseases Valine Liter Prodrug Infectious Diseases Herpes simplex virus Therapeutic drug monitoring Valacyclovir business |
| Zdroj: | Antimicrob Agents Chemother |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | Acyclovir is an antiviral currently used for the prevention and treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. This study aimed to characterize the pharmacokinetics (PK) of acyclovir and its oral prodrug valacyclovir to optimize dosing in children. Children receiving acyclovir or valacyclovir were included in this study. PK were described using nonlinear mixed-effect modeling. Dosing simulations were used to obtain trough concentrations above a 50% inhibitory concentration for HSV or VZV (0.56 mg/liter and 1.125 mg/liter, respectively) and maximal peak concentrations below 25 mg/liter. A total of 79 children (212 concentration-time observations) were included: 50 were taking intravenous (i.v.) acyclovir, 22 were taking oral acyclovir, and 7 were taking both i.v. and oral acyclovir, 57 for preventive and 22 for curative purposes. A one-compartment model with first-order elimination best described the data. An allometric model was used to describe body weight effect, and the estimated glomerular filtration rate (eGFR) was significantly associated with acyclovir elimination. To obtain target maximal and trough concentrations, the more suitable initial acyclovir i.v. dose was 10 mg/kg of body weight/6 h for children with normal renal function (eGFR ≤ 250 ml/min/1.73 m(2)) and 15 to 20 mg/kg/6 h for children with augmented renal clearance (ARC) (eGFR > 250 ml/min/1.73 m(2)). The 20-mg/kg/8 h dose for oral acyclovir and valacyclovir produced effective concentrations in more than 75% of children; however, a 15-mg/kg/6 h dose, if possible, is preferred. These doses should be prospectively confirmed, and therapeutic drug monitoring could be used to refine them individually. (This study has been registered at ClinicalTrials.gov under identifier NCT02539407.) |
| Databáze: | OpenAIRE |
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