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Pharmacologic Studies of Methotrexate in Cancer Patients With Uropathy

Yoichi Ojima, MD, PhD; Leonard L. Anderson, MS; Gerald J. Collins, BS; Richard A. Oberfield, MD; Robert D. Sullivan, MD, FACP
Arch Surg. 1970;100(2):173-177. doi:10.1001/archsurg.1970.01340200061014.
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Methotrexate (4-amino-N10-methylpteroylglutamic acid) is well tolerated by most patients using the usual dosage schedules and routes of administration (oral, intravenous, and intramuscular), as previously described by Farber et al,1 Burchenal et al,2 Schoenbach et al,3 and others. Moreover, more recent studies of the clinical effects of methotrexate when given by several dose schedules and routes of administration (ie, continuous intravenous and intra-arterial infusion, intrathecal and intraventricular injections) have shown that this antimetabolite is well tolerated to the extent of acceptable toxicity.4-8

We have previously reported the clinical effects of the protracted administration of methotrexate,9 the general pharmacodynamics in the human,10 and studies of methotrexate in the human central nervous system.11 A total of 259 patients was included in these clinical pharmacologic investigations. During these studies it became apparent that in patients with impaired renal function, the methotrexate serum levels and urinary


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