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Pharmacokinetics of DX‐8951 in pediatric cancer patients
Author(s) -
Trinh M.,
Colucci P.,
Kamida M.,
Danna M.,
De Jager R.,
Trippett T.,
Ducharme M. P.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.223
Subject(s) - medicine , pharmacokinetics , volume of distribution , population , nonmem , clinical pharmacology , pediatrics , pharmacology , environmental health
Background/Aim To characterize the pharmacokinetics (PK) of DX‐8951 in pediatric cancer patients. Methods Plasma PK parameters for DX‐8951 were calculated using noncompartmental and population (NONMEM ® ) PK analyses. Design Phase I dose escalation study of intravenous (i.v.) DX‐8951f. Settings Patients (Pts) were treated at the hospital. Participants 59 Pts aged less than 25 years of age. Intervention Five patient cohorts received a 30 min i.v. infusion daily, for five days, at doses of 0.25, 0.35, 0.45, 0.55 and 0.65 mg/m 2 . Results A 2‐compartment PK model explained the PKs of DX‐8951 in plasma. Clinical parameters used as covariates to explain the PKs of DX‐8951 were gender, age, weight and calculated creatinine clearance (CCL) on CL, and gender and weight on the central volume of distribution (Vc). Of these covariates, age seems to be the clinically relevant one for the clearance of DX‐8951. Clearance (CL) was faster in Pts≤ 10 years of age, and fell by approximately 50% after that age, attaining adult CL values. Conclusions Dose adjustments based on weight for i.v. administered DX‐8951f could be required for patients aged less than 10 years of age. Clinical Pharmacology & Therapeutics (2005) 77 , P86–P86; doi: 10.1016/j.clpt.2004.12.223