Abstract
Purpose
Temozolomide pharmacokinetics were evaluated in children receiving concurrent O6-benzylguanine (O6BG), which enhanced the hematological toxicity of temozolomide.
Methods
Temozolomide was administered orally, daily for 5 days starting at 28 mg/m2 per day with escalations to 40, 55, 75 and 100 mg/m2 per day with O6BG intravenously daily for 5 days at doses of 60, 90 or 120 mg/m2 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/m2) 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 O6BG with temozolomide does not appear to be the result of a pharmacokinetic interaction between the agents.
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Meany, H.J., Warren, K.E., Fox, E. et al. Pharmacokinetics of temozolomide administered in combination with O6-benzylguanine in children and adolescents with refractory solid tumors. Cancer Chemother Pharmacol 65, 137–142 (2009). https://doi.org/10.1007/s00280-009-1015-8
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DOI: https://doi.org/10.1007/s00280-009-1015-8