Increased teniposide clearance with concomitant anticonvulsant therapy

D. K. Baker, M. V. Relling, C. H. Pui, Michael Christensen, W. E. Evans, J. H. Rodman

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)311-315
Number of pages5
JournalJournal of Clinical Oncology
Volume10
Issue number2
DOIs
StatePublished - Jan 1 1992

Fingerprint

Teniposide
Anticonvulsants
Therapeutics
Pediatrics
Phenytoin
Phenobarbital
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Protein Binding
Pharmacokinetics
High Pressure Liquid Chromatography
Control Groups

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Increased teniposide clearance with concomitant anticonvulsant therapy. / Baker, D. K.; Relling, M. V.; Pui, C. H.; Christensen, Michael; Evans, W. E.; Rodman, J. H.

In: Journal of Clinical Oncology, Vol. 10, No. 2, 01.01.1992, p. 311-315.

Research output: Contribution to journalArticle

Baker, D. K. ; Relling, M. V. ; Pui, C. H. ; Christensen, Michael ; Evans, W. E. ; Rodman, J. H. / Increased teniposide clearance with concomitant anticonvulsant therapy. In: Journal of Clinical Oncology. 1992 ; Vol. 10, No. 2. pp. 311-315.
@article{5690b81201ad4d188c05333a22e57fb4,
title = "Increased teniposide clearance with concomitant anticonvulsant therapy",
abstract = "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.",
author = "Baker, {D. K.} and Relling, {M. V.} and Pui, {C. H.} and Michael Christensen and Evans, {W. E.} and Rodman, {J. H.}",
year = "1992",
month = "1",
day = "1",
doi = "10.1200/JCO.1992.10.2.311",
language = "English (US)",
volume = "10",
pages = "311--315",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "2",

}

TY - JOUR

T1 - Increased teniposide clearance with concomitant anticonvulsant therapy

AU - Baker, D. K.

AU - Relling, M. V.

AU - Pui, C. H.

AU - Christensen, Michael

AU - Evans, W. E.

AU - Rodman, J. H.

PY - 1992/1/1

Y1 - 1992/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0026515548&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026515548&partnerID=8YFLogxK

U2 - 10.1200/JCO.1992.10.2.311

DO - 10.1200/JCO.1992.10.2.311

M3 - Article

VL - 10

SP - 311

EP - 315

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 2

ER -