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The pharmacology of orally administered chemotherapy: A reappraisal
Author(s) -
Poplack David G.,
Balis Frank M.,
Zimm Solomon
Publication year - 1986
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19860715)58:2+<473::aid-cncr2820581311>3.0.co;2-0
Subject(s) - medicine , clinical pharmacology , methotrexate , chemotherapy , pharmacology , dosing , oral administration , pharmacokinetics , bioavailability , drug , route of administration
Rational treatment of pediatric malignancies requires a detailed knowledge of the clinical pharmacology of those antineoplastic agents used therapeutically. A number of different agents are administered by the oral route. Recently, the clinical pharmacology of 6‐mercaptopurine (6‐MP) and methotrexate (MTX), the two agents that are the mainstay of maintenance chemotherapy in acute lymphoblastic leukemia (ALL), were investigated. Studies of oral 6‐MP indicate that, contrary to previous information, the bio‐ availability of this drug is relatively poor after oral administration, and that plasma 6‐MP concentrations achieved after uniform oral dosing are highly variable. Similarly, study of the pharmacology of orally administered MTX indicates that there is little correlation between MTX dose and the peak serum level achieved. These findings suggest that some patients may not be exposed to adequate systemic concentrations of 6‐MP and/or MTX after oral administration, and raise the possibility that the development of relapse in some patients with ALL may be the result of a pharmacologic failure of oral maintenance therapy. A comprehensive prospective study of the clinical pharmacology of MTX and 6‐MP in patients with ALL undergoing maintenance chemotherapy is currently in progress. Cancer 58:473‐480, 1986.

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