Population pharmacokinetics of intravenous ondansetron in oncology and surgical patients aged 1-48 months.

PURPOSE

Until 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.

METHODS

The 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.

RESULTS

Ondansetron 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.

CONCLUSIONS

The 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.