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 grou...

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Bibliographic Details
Published in:European journal of clinical pharmacology 2010, Vol.66 (1), p.77-86
Main Authors: Mondick, John T, Johnson, Brendan M, Haberer, Lynda J, Sale, Mark E, Adamson, Peter C, Coté, Charles J, Croop, James M, Russo, Mark W, Barrett, Jeffrey S, Hoke, J. Frank
Format: Article
Language:English
Subjects:
Age
Anesthesia, General - adverse effects
Antiemetics - administration & dosage
Antiemetics - pharmacokinetics
Antiemetics - therapeutic use
Antineoplastic Agents - adverse effects
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Child, Preschool
Children & youth
Computer Simulation
Drug therapy
Female
Humans
Infant
Injections, Intravenous
Male
Medical sciences
Metabolic Clearance Rate
Nausea
Nausea - chemically induced
Nausea - prevention & control
Ondansetron - administration & dosage
Ondansetron - pharmacokinetics
Ondansetron - therapeutic use
Pharmacokinetics and Disposition
Pharmacology
Pharmacology. Drug treatments
Pharmacology/Toxicology
Serotonin Antagonists - administration & dosage
Serotonin Antagonists - pharmacokinetics
Serotonin Antagonists - therapeutic use
Surgery
Vomiting
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Summary: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/kg⁰.⁷⁵ 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.
ISSN:0031-6970
1432-1041
DOI:10.1007/s00228-009-0730-8