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Increased teniposide clearance with concomitant anticonvulsant therapy.
D K Baker1, M V Relling, C H Pui
1Pharmacokinetics and Pharmacodynamics Section, St Jude Children's Research Hospital, Memphis, TN 38105.
Summary
Concomitant use of anticonvulsants like phenobarbital or phenytoin significantly increases teniposide clearance in pediatric patients. This pharmacokinetic interaction may reduce the efficacy of teniposide chemotherapy.
Area of Science:
- Pharmacokinetics
- Pediatric Oncology
- Drug Interactions
Background:
- Teniposide is a chemotherapy agent used in treating acute lymphocytic leukemia.
- Anticonvulsant medications are often co-administered in pediatric patients undergoing cancer treatment.
- Potential pharmacokinetic interactions between teniposide and anticonvulsants require investigation.
Purpose of the Study:
- To evaluate a potential pharmacokinetic interaction between teniposide and anticonvulsant medications.
- To assess the impact of anticonvulsants on teniposide systemic clearance in pediatric patients.
Main Methods:
- Systemic clearance of teniposide was determined in pediatric patients with acute lymphocytic leukemia receiving anticonvulsants.
- Plasma concentrations of teniposide were measured using high-performance liquid chromatography (HPLC).
- Data were analyzed using a two-compartment model and compared to a control group without anticonvulsants.
Main Results:
- Systemic clearance of teniposide was significantly higher (2- to 3-fold increase) in patients receiving anticonvulsants (32 mL/min/m2) compared to controls (13 mL/min/m2).
- P-value < .001 indicated a statistically significant difference in clearance.
- Clearance values in control patients were consistent with previously published data.
Conclusions:
- Concomitant phenobarbital or phenytoin therapy significantly increases teniposide systemic clearance.
- This substantial reduction in systemic exposure may compromise teniposide's therapeutic efficacy.
- Further studies are warranted to adjust dosing regimens when teniposide is used with these anticonvulsants.