Population Pharmacokinetics of Digoxin in Pediatric Patients A. Martı ´n-Sua ´rez,* A. C. Falcao,† M. Outeda,‡ F. J. Herna ´ndez,§ M. C. Gonza ´lez,  M. Quero,  I. Arranz,§ and J. M. Lanao* *Department of Pharmacy and Pharmaceutical Technology, University of Salamanca, Spain; †Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Portugal; ‡Pharmacy Service, Juan Canalejo Hospital, La Coruña, Spain; and §Biochemical and Cardiopediatric Services, Ramón y Cajal Hospital, Madrid, Spain Summary: Digoxin pharmacokinetics were studied in a pediatric population with an age range of 6 days to 1 year using the population pharmacokinetic approach. Digoxin data were analyzed by mixed-effects modeling according to a one-compartment steady-state pharmacokinetic model using NONMEM software. The final model se- lected for the population prediction of digoxin clearance in pediatric patients was as follows: Cl(L/h/kg)  0.237(1 + 0.094 * AGE (months)) Individual empirical Bayesian estimates were generated on the basis of the popu- lation estimates and were used to correlate the optimum dose of digoxin and patient age according to the following equation: Dose(g/kg/day)  9.022 + 0.712 * AGE (months) This equation and its derived nomogram may be used for the initial dosing of digoxin in children aged between 0 and 1 year. The use of this nomogram in routine monitoring requires further pharmacokinetic and clinical validation. Key Words: Di- goxin—Population pharmacokinetics—Pediatric patients. Digoxin is a drug widely used for the management of cardiac rhythm disturbances in neonates, infants, and children. It has a very narrow therapeutic index and dis- plays large inter- and intra-patient pharmacokinetic vari- ability, meaning that its serum levels must be monitored. Its pharmacokinetics have been studied in depth in adults, but there are few works relating to the behavior of the drug in pediatric populations. In this type of patient, it is difficult to collect data other than the sparse retro- spective information obtained from routine monitoring of concentrations; hence, pharmacokinetic studies using population methodology are very appropriate. Some changes in digoxin disposition appear to be strongly correlated with normal physiologic develop- ment during the first year of life (1–6). For this reason, the relationship between digoxin pharmacokinetic pa- rameters and age in this population should be known to obtain appropriate dosage schedules in clinical practice. Thus, the aim of our present work was to study the popu- lation pharmacokinetics of digoxin in pediatric patients aged less than 1 year in an attempt to obtain a model able to describe, as simply as possible, the evolution of di- goxin concentrations during the first year of life in this population. MATERIALS AND METHODS A complete retrospective study was carried out in 51 pediatric patients from two different hospitals. All were Received April 26, 2001; accepted April 26, 2002. Address correspondence and reprint requests to Prof. José M. Lanao, Departamento Farmacia y Tecnología Farmacéutica, Facultad de Far- macia, Campus Miguel de Unamuno, 37007 Salamanca, Spain; E-mail: jmlanao@gugu.usal.es Therapeutic Drug Monitoring 24:742–745 © 2002 Lippincott Williams & Wilkins, Inc., Philadelphia 742