Journal of Clinical Oncology, Vol 10, 311-315, Copyright © 1992 by American Society of Clinical Oncology
Increased teniposide clearance with concomitant anticonvulsant therapy
DK Baker, MV Relling, CH Pui, ML Christensen, WE Evans and JH Rodman
Pharmacokinetics and Pharmacodynamics Section, St Jude Children's Research Hospital, Memphis, TN 38105.
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 less than .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.
