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Pharmacokinetics of temozolomide administered in combination with O6-benzylguanine in children and adolescents with refractory solid tumors.

Abstract：

PURPOSE:Temozolomide pharmacokinetics were evaluated in children receiving concurrent O(6)-benzylguanine (O(6)BG), which enhanced the hematological toxicity of temozolomide. METHODS:Temozolomide was administered orally, daily for 5 days starting at 28 mg/m(2) per day with escalations to 40, 55, 75 and 100 mg/m(2) per day with O(6)BG intravenously daily for 5 days at doses of 60, 90 or 120 mg/m(2) per day. Plasma samples were drawn over 48 h after the day 5 dose. Temozolomide was quantified with a validated HPLC/tandem mass spectroscopic assay. RESULTS:Temozolomide was rapidly absorbed (mean T (max), 2.1 h). The mean apparent clearance (CL/F) (96 mL/min/m(2)) was similar to the CL/F for temozolomide alone and was not age- or gender-dependent. There was minimal inter-patient variability. CONCLUSIONS:The enhanced hematologic toxicity resulting from combining O(6)BG with temozolomide does not appear to be the result of a pharmacokinetic interaction between the agents.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

Meany HJ,Warren KE,Fox E,Cole DE,Aikin AA,Balis FM

doi

10.1007/s00280-009-1015-8

subject

Has Abstract

pub_date

2009-12-01 00:00:00

pages

137-42

issue

1

eissn

0344-5704

issn

1432-0843

journal_volume

65

pub_type

杂志文章

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