• John T Mondick, Brendan M Johnson, Lynda J Haberer, Mark E Sale, Peter C Adamson, Charles J Coté, James M Croop, Mark W Russo, Jeffrey S Barrett, and J Frank Hoke.
• Metrum Institute, Tariffville, CT 06081, USA. johnm@metrumrg.com
• Eur. J. Clin. Pharmacol. 2010 Jan 1; 66 (1): 77-86.

PurposeUntil recently, ondansetron was approved for the prevention of nausea and vomiting only in patients older than 2 years. However, as the use of ondansetron in patients younger than 2 years had been documented, characterization of ondansetron pharmacokinetics in this younger pediatric age group was warranted.MethodsThe pharmacokinetics of intravenously administered ondansetron were evaluated in oncology and surgical patients aged 1-48 months. Pooled data from 124 patients, including 745 pharmacokinetic samples, were analyzed using nonlinear mixed-effects modeling.ResultsOndansetron pharmacokinetics were described by a two-compartment model. Body-size effects on ondansetron disposition were accounted for via standard allometric relationships, normalized to 10.4 kg. A maturation process with a half-life of approximately 4 months was incorporated to describe a decrease in clearance (CL) in infants. Clearance [95% confidence interval (CI)] for a typical patient was 1.53 (1.34-1.78) L/h/kg(0.75) with an interindividual variability of 56.8%. Ondansetron CL was reduced by 31%, 53%, and 76% for the typical 6-month-, 3-month-, and 1-month-old patient, respectively. Simulations showed that an ondansetron dose of 0.1 mg/kg in children younger than 6 months produced exposure similar to a 0.15-mg/kg dose in older children.ConclusionsThe population pharmacokinetic analysis of ondansetron allows for characterization of individual patients based on body weight and age. It is recommended that patients younger than 4 months receiving ondansetron be closely monitored.

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