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.
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.
Authors: Warren P Mason; Mary Macneil; Petr Kavan; Jacob Easaw; David Macdonald; Brian Thiessen; Shweta Urva; Zarnie Lwin; Lynn McIntosh; Elizabeth Eisenhauer Journal: Invest New Drugs Date: 2011-12-09 Impact factor: 3.850
Authors: Cynthia M McCully; Devang Pastakia; John Bacher; Marvin L Thomas; Emilie A Steffen-Smith; Kadharbatcha Saleem; Robert F Murphy; Stuart Walbridge; Lauren Brinster; Brigitte C Widemann; Katherine E Warren Journal: Comp Med Date: 2013-08 Impact factor: 0.982
Authors: Stephen T Keir; John M Maris; C Patrick Reynolds; Min H Kang; E Anders Kolb; Richard Gorlick; Richard Lock; Hernan Carol; Christopher L Morton; Jianrong Wu; Raushan T Kurmasheva; Peter J Houghton; Malcolm A Smith Journal: Pediatr Blood Cancer Date: 2013-01-17 Impact factor: 3.167
Authors: Eric S Schafer; Rachel E Rau; Stacey L Berg; Xiaowei Liu; Charles G Minard; Alexander J R Bishop; J Carolina Romero; M John Hicks; Marvin D Nelson; Stephan Voss; Joel M Reid; Elizabeth Fox; Brenda J Weigel; Susan M Blaney Journal: Pediatr Blood Cancer Date: 2019-11-14 Impact factor: 3.838
Authors: A Laura Nijstad; Shelby Barnett; Arief Lalmohamed; Inez M Bérénos; Elizabeth Parke; Vickyanne Carruthers; Deborah A Tweddle; Jordon Kong; C Michel Zwaan; Alwin D R Huitema; Gareth J Veal Journal: Eur J Cancer Date: 2021-12-02 Impact factor: 9.162