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- Title
Pharmacokinetics of temozolomide administered in combination with O6-benzylguanine in children and adolescents with refractory solid tumors.
- Authors
Meany HJ; Warren KE; Fox E; Cole DE; Aikin AA; Balis FM; Meany, Holly J; Warren, Katherine E; Fox, Elizabeth; Cole, Diane E; Aikin, Alberta A; Balis, Frank M
- Abstract
<bold>Purpose: </bold>Temozolomide pharmacokinetics were evaluated in children receiving concurrent O(6)-benzylguanine (O(6)BG), which enhanced the hematological toxicity of temozolomide.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Publication
Cancer Chemotherapy & Pharmacology, 2009, Vol 65, Issue 1, p137
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/s00280-009-1015-8