| Title | Population pharmacokinetics of acyclovir in children and young people with malignancy after administration of intravenous acyclovir or oral valacyclovir. | | Author(s) | Zeng L, Nath CE, Blair EY, Shaw PJ, Stephen K, Earl JW, Coakley JC, McLachlan AJ | | Institution | Faculty of Pharmacy, University of Sydney, NSW 2006, Australia; Departments of Biochemistry and Oncology, The Children's Hospital at Westmead, NSW 2145, Australia; Department of Paediatrics and Child Health, University of Sydney, NSW 2006, Australia; Centre for Education and Research on Ageing, Concord Hospital, Concord, NSW 2139, Australia. | | Source | Antimicrob Agents Chemother 2009 May 4. | | Abstract | Acyclovir is effective in the prevention and treatment of herpes simplex (HSV) and varicella zoster (VZV) virus infections. The study aim was to characterise the population pharmacokinetics of acyclovir following intravenous acyclovir and oral valacyclovir in young people with malignancy. Plasma acyclovir concentration-time data was collected from 43 patients (age:9 months-20 years) who had been given multiple doses of acyclovir (5mg/kg) and/or valacyclovir (10mg/kg). Nonlinear mixed-effects modelling was employed to analyse acyclovir population pharmacokinetics and identify influential covariates. Simulations (n=1000) were conducted to explore the relevance of the current doses to maintain acyclovir concentrations above the recommended IC50 for HSV and VZV (0.56mg/L and 1.125mg/L, respectively) for greater than 12h. A one-compartment pharmacokinetic model with first-order elimination best described the acyclovir concentration-time data. Population mean estimates of clearance(CL), volume of distribution(V), absorption rate(ka) and bioavailability(F) were 3.55L/h, 7.36L, 0.63h(-1) and 0.60, respectively. Inclusion of body weight and estimated creatinine clearance (CLCR) in the final model reduced the inter-individual variability in CL and V from 61% to 24% and from 75% to 36%, respectively. Simulations revealed that using current doses, maximal efficacy can be achieved in over 45% of patients weighing 25-50kg and with CLCR of 2.0-4.0L/h/m(2), but only in a much smaller proportion of patients of low weight (10 kg) with high CLCR (5.5 L/h/m(2)), suggesting that higher doses are required for this subgroup. This validated population pharmacokinetic model for acyclovir may be used to develop dosing guidelines for safe and effective antiviral therapy in young people with malignancy. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19414579 |
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