PMID: 9188769Jan 1, 1997Paper

Alterations in methotrexate pharmacokinetics by naproxen in the rat as measured by microdialysis

Life Sciences
P O EkstrømL Slørdal

Abstract

Reports of a potentially life-threatening interaction between the antifolate methotrexate (MTX) and drugs belonging to the NSAID class instigated a study of MTX pharmacokinetics by a microdialysis technique in the presence and absence of the NSAID naproxen in anesthetized rats. After pretreatment with naproxen, the animals received either 750 or 1,000 mg/kg MTX as a 6 h continuous intravenous infusion. During infusions, microdialysis effluents were obtained from probes situated intravenously, intrahepatically and intrarenally. In all three compartments, time-concentration AUCs for both MTX and its major extracellular metabolite, 7-hydroxymethotrexate (7-OH-MTX), increased about two-fold in the presence of naproxen. The mechanisms responsible for the MTX-NSAID interaction are briefly discussed. The study demonstrate that the microdialysis technique offers a means to investigate pharmacokinetic drug-drug interactions.

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Citations

Jun 7, 2005·Toxicology and Applied Pharmacology·Hsiu-Mei ChiangPei-Dawn Lee Chao
Jun 16, 2012·Toxicology and Applied Pharmacology·Shih-Ying YangYu-Chi Hou
Jan 6, 1999·Journal of Pharmaceutical Sciences·D K HansenC E Lunte
Nov 6, 2002·Journal of Experimental Therapeutics & Oncology·Mary J JohansenTimothy Madden

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