INCREASED TENIPOSIDE CLEARANCE WITH CONCOMITANT ANTICONVULSANT THERAPY

被引:52
作者
BAKER, DK
RELLING, MV
PUI, CH
CHRISTENSEN, ML
EVANS, WE
RODMAN, JH
机构
[1] ST JUDE CHILDRENS RES HOSP, DIV PHARMACEUT, PHARMACOKINET & PHARMACODYNAM SECT, 332 N LAUDERDALE, MEMPHIS, TN 38101 USA
[2] ST JUDE CHILDRENS RES HOSP, DEPT HEMATOL ONCOL, MEMPHIS, TN 38101 USA
[3] UNIV TENNESSEE CTR HLTH SCI, DEPT CLIN PHARM, CTR PEDIAT PHARMACOKINET & THERAPEUT, MEMPHIS, TN 38163 USA
[4] UNIV TENNESSEE CTR HLTH SCI, DEPT PEDIAT, MEMPHIS, TN 38163 USA
关键词
D O I
10.1200/JCO.1992.10.2.311
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: A possible pharmacokinetic interaction between teniposide and anticonvulsant medications was evaluated in pediatric patients. Patients and Methods: The systemic clearance of teniposide was determined in six pediatric patients with acute lymphocytic leukemia receiving concomitant therapy with anticonvulsants. Clearance was then compared with a control group of patients treated with the same protocol therapy and matched for age at diagnosis, sex, and race but not receiving anticonvulsants or other agents known to induce hepatic metabolism or alter protein binding of drugs. Eight blood samples were obtained during and after 4-hour infusions of teniposide, and plasma concentrations were measured by a specific high-performance liquid chromatography (HPLC) assay. A two-compartment model was fitted to each subject's data. Results: The mean systemic clearance (range) for the six anticonvulsant-treated patients studied during 22 courses of therapy was 32 mL/min/m2 (range, 21 to 54 mL/min/m2), significantly higher (P < .001) than the mean value of 13 mL/min/m2 (range, 7 to 17 mL/min/m2) for the control patients studied during 26 courses of therapy. Clearance estimates for control patients were similar to previously published values for pediatric patients. Conclusion: These data indicate that the systemic clearance of teniposide is consistently increased two- to three-fold by concomitant phenobarbital or phenytoin therapy. The consequent substantial reduction in systemic exposure may reduce teniposide's efficacy.
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页码:311 / 315
页数:5
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