Aims: To develop a population pharmacokinetic model for penciclovir (famciclovir is a prodrug of penciclovir) in adults and children and suggest an appropriate dose for children. Furthermore, to develop a limited sampling design based on sampling windows for three different paediatric age groups (1-2, 2-5 and 5-12 years) using an adequate number of subjects for future pharmacokinetic studies. Methods: Penciclovir plasma data from six different adult and paediatric studies were supplied by Novartis. Population pharmacokinetic modelling was undertaken in NONMEM version VI. Simulations in MATLAB were used to select an oral paediatric dose that gives similar exposure to 500 mg in adults. Optimal sampling times and sampling windows were obtained in MATLAB and simulations in NONMEM were used to select adequate sample sizes for three paediatric age groups. Results: A two-compartment, first-order absorption model with an absorption lag time, allometric weight models on V1, V 2 and Q, and an allometric weight model, age and creatinine clearance as covariates on CL adequately describe the pharmacokinetics of penciclovir in adults and children. Estimated CL (l h-1 70 kg-1) and Vss (l.70 kg-1) were 31.2 and 83.1, respectively. An oral dose of 10 mg kg-1 body weight in children was predicted to give similar exposure as 500 mg in adults. A single sampling windows design (0.25-0.4, 0.5-1, 1.25-1.75, 2.75-3.5 and 7.25-8 h) for five samples per subject and 10 subjects in each of the paediatric age groups is recommended for future studies. Conclusions: A population pharmacokinetic model of penciclovir in adults and children has been developed. A prospective study design, including dose adjustment, cohort size and blood sampling design has been recommended. © 2009 The British Pharmacological Society.