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Methotrexate Excretion Patterns and Renal Toxicity:  After Intravenous Injection or Arterial Infusion

Devendra D. Patel, MS, FRCS; Fred R. Morgenthaler, MD; Amir M. Khazei, MD; Robert Grimaldi, MS; Elton Watkins Jr., MD
Arch Surg. 1969;98(3):305-308. doi:10.1001/archsurg.1969.01340090081012.
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The cancer chemotherapy group at the Lahey Clinic Foundation has been active in using regional intraarterial infusion chemotherapy of far-advanced solid tumors in various body regions.1 Problems have been encountered during regional therapy with the folic acid antagonist, methotrexate. If methotrexate is administered regionally in patients with impaired renal function, systemic toxic reactions to the drug are seen at low levels of dosage, presumably because of impaired excretion of drug by the kidneys. In the individual with normal renal function, no methotrexate is detectable in the serum shortly after an intravenous dose.2 When renal function is impaired, appreciable amounts of the drug are present in the serum, even after 48 hours.3 The current experiments were carried out to study the dynamics of enhanced drug toxicity observed in association with impaired renal function.

Experimental Procedure  Female mongrel dogs weighing between 20 and 25 kg (44 and 55 1b)

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