Abstract:
: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 bioavailability 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.
journal_name
Cancerjournal_title
Cancerauthors
Poplack DG,Balis FM,Zimm Sdoi
10.1002/1097-0142(19860715)58:2+<473::aid-cncr2820subject
Has Abstractpub_date
1986-07-15 00:00:00pages
473-80issue
2 Suppleissn
0008-543Xissn
1097-0142journal_volume
58pub_type
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