Chronopharmacokinetics of oral methotrexate and 6-mercaptopurine

Is there diurnal variation in the disposition of antileukemic therapy?

Frank M. Balis, Susan L. Jeffries, Beverly Lange, Robert F. Murphy, Karen M. Doherty, Carola A.S. Arndt, Nicolette Luery, David G. Poplack

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The chronopharmacokinetics of the orally administered antileukemic drugs, 6-mercaptopurine and methotrexate, were examined in 13 children with acute lymphoblastic leukemia (ALL) to establish if there is a pharmacokinetic basis for the lower relapse rate associated with adminis-tration of these agents in the evening. Children with ALL in complete remission had plasma drug concentrations monitored for 8 h following an oral dose of either meth-otrexate or 6-mercaptopurine administered in the morn-ing (8 a.m.) and the evening (8 p.m.). Total drug exposure to oral methotrexate, as measured by the mean area under the plasma concentration-time curve (AUC), was 2.75 p.M o h following the morning dose and 2.77 p.M o h in the evening. For 6-mercaptopurine, the mean morning AUC (198 ng o h/ml) was higher than that following the evening dose (167 ng o h/ml) (p > 0.05); but compared to the wide interpatient variability observed with this drug, this 20% difference is not likely to be clinically significant. These results indicate that the suggested benefit of evening drug administration is not likely to be a result of diurnal variation in drug disposition.

Original languageEnglish (US)
Pages (from-to)324-326
Number of pages3
JournalAmerican Journal of Pediatric Hematology/Oncology
Volume11
Issue number3
StatePublished - 1989
Externally publishedYes

Fingerprint

6-Mercaptopurine
Methotrexate
Pharmaceutical Preparations
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Area Under Curve
Therapeutics
Chronopharmacokinetics
Pharmacokinetics
Recurrence

Keywords

  • 6-Mercaptopurine
  • Acute lymphoblastic leukemia
  • Diurnal variation
  • Methotrexate
  • Phamacokinetics

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Pediatrics, Perinatology, and Child Health

Cite this

Chronopharmacokinetics of oral methotrexate and 6-mercaptopurine : Is there diurnal variation in the disposition of antileukemic therapy? / Balis, Frank M.; Jeffries, Susan L.; Lange, Beverly; Murphy, Robert F.; Doherty, Karen M.; Arndt, Carola A.S.; Luery, Nicolette; Poplack, David G.

In: American Journal of Pediatric Hematology/Oncology, Vol. 11, No. 3, 1989, p. 324-326.

Research output: Contribution to journalArticle

Balis, Frank M. ; Jeffries, Susan L. ; Lange, Beverly ; Murphy, Robert F. ; Doherty, Karen M. ; Arndt, Carola A.S. ; Luery, Nicolette ; Poplack, David G. / Chronopharmacokinetics of oral methotrexate and 6-mercaptopurine : Is there diurnal variation in the disposition of antileukemic therapy?. In: American Journal of Pediatric Hematology/Oncology. 1989 ; Vol. 11, No. 3. pp. 324-326.
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abstract = "The chronopharmacokinetics of the orally administered antileukemic drugs, 6-mercaptopurine and methotrexate, were examined in 13 children with acute lymphoblastic leukemia (ALL) to establish if there is a pharmacokinetic basis for the lower relapse rate associated with adminis-tration of these agents in the evening. Children with ALL in complete remission had plasma drug concentrations monitored for 8 h following an oral dose of either meth-otrexate or 6-mercaptopurine administered in the morn-ing (8 a.m.) and the evening (8 p.m.). Total drug exposure to oral methotrexate, as measured by the mean area under the plasma concentration-time curve (AUC), was 2.75 p.M o h following the morning dose and 2.77 p.M o h in the evening. For 6-mercaptopurine, the mean morning AUC (198 ng o h/ml) was higher than that following the evening dose (167 ng o h/ml) (p > 0.05); but compared to the wide interpatient variability observed with this drug, this 20{\%} difference is not likely to be clinically significant. These results indicate that the suggested benefit of evening drug administration is not likely to be a result of diurnal variation in drug disposition.",
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