Pharmacokinetics of dactinomycin in a pediatric patient population: a United Kingdom Children's Cancer Study Group Study
Autor: | Ann Elsworth, Gareth J. Veal, Carol Beane, Julie Errington, Julia C. Chisholm, Alan V. Boddy, Fiona Waters, Heather P. McDowell, Michael Cole, Karen Howe, Juliet Hale, Adam Glaser, Yvonne Wright, Ross Pinkerton, Sue Hemsworth, Kathy Pritchard-Jones, Annie Parry, Gail Jenner, James Nicholson, Bernadette Brennan, Andrew D.J. Pearson |
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Rok vydání: | 2005 |
Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Pediatrics Time Factors Adolescent Fever Metabolic Clearance Rate Population Infections Gastroenterology Mass Spectrometry Bolus (medicine) Pharmacokinetics Internal medicine Neoplasms medicine Humans Dosing Ifosfamide education Child Infusions Intravenous Antineoplastic Agents Alkylating education.field_of_study Analysis of Variance Dactinomycin Antibiotics Antineoplastic Dose-Response Relationship Drug business.industry Confidence interval Dose–response relationship Oncology Area Under Curve Child Preschool Toxicity Female business medicine.drug Chromatography Liquid |
Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 11(16) |
ISSN: | 1078-0432 |
Popis: | Purpose: Dactinomycin (actinomycin D) is an antitumor antibiotic used routinely to treat certain pediatric and adult cancers. Despite concerns over the incidence of toxicity, little is known about the pharmacology of dactinomycin. A study was done to investigate dactinomycin pharmacokinetics in children. Experimental Design: Dactinomycin was administered to 31 patients by bolus i.v. infusion, at doses of 0.70 to 1.50 mg/m2. Plasma concentrations were determined by liquid chromatography-mass spectrometry up to 24 hours after drug administration and National Cancer Institute Common Toxicity Criteria was assessed. Results: Pharmacokinetic data analysis suggested that a three-compartment model most accurately reflected dactinomycin pharmacokinetics. However, there was insufficient data available to fully characterize this model. A median peak plasma concentration (Cmax) of 25.1 ng/mL (range, 3.2-99.2 ng/mL) was observed at 15 minutes after administration. The median exposure (AUC0-6), determined in 16 patients with sampling to 6 hours, was 2.67 mg/L.min (range, 1.12-4.90 mg/L.min). After adjusting for body size, AUC0-6 and Cmax were positively related to dose (P = 0.03 and P = 0.04, respectively). Patients who experienced any level of Common Toxicity Criteria grade had a 1.46-fold higher AUC0-6, 95% confidence interval (1.02-2.09). AUC0-6 was higher in patients Conclusions: Data presented suggest that dosing of dactinomycin based on surface area is not optimal, either in younger patients in whom the risk of toxicity is greater, or in older patients where doses are capped. |
Databáze: | OpenAIRE |
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