Increased teniposide clearance with concomitant anticonvulsant therapy.
OBJECTIVE
A possible pharmacokinetic interaction between teniposide and anticonvulsant medications was evaluated in pediatric patients.


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.


CONCLUSIONS
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.
Baker
D K
DK
Pharmacokinetics and Pharmacodynamics Section, St Jude Children's Research Hospital, Memphis, TN 38105.
Relling
M V
MV
Pui
C H
CH
Christensen
M L
ML
Evans
W E
WE
Rodman
J H
JH
D000293:Adolescent; D000927:Anticonvulsants / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D013713:Teniposide / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000927:Anticonvulsants; D010672:Phenytoin; D013713:Teniposide; D010634:Phenobarbital