Potentiated Decrease of Plasma Folate Levels Caused by the Coadministration of Folic Acid in Rats Treated with Methotrexate.

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概要

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• The decrease of plasma 5-methyltetrahydrofolic acid (5-MF) levels, postulated as an indicator of folate status, was studied following the administration of both methotrexate (MTX) alone and MTX with folic acid (FA) using rats as our experimental model. Blood and urine samples were serially collected over a 9 hr period after the administration of MTX, MTX with FA and from a control group to examine the plasma kinetics and the renal clearance of 5-MF. The pharmacokinetics of MTX and the plasma protein binding of 5-MF were also examined. The concentrations of these analytes were assayed using high performance liquid chromatography (HPLC). MTX administration produced decreased plasma 5-MF levels. This observed decrease was potentiated by oral FA administration, suggesting that the folate status was more severely altered by the coadministration of FA. The renal clearance of 5-MF also increased dose-dependently with FA (0.05-5 mg/kg) coadministration. The plasma protein binding of 5-MF was not affected by the FA administration, which indicates that the fraction of 5-MF that was filtered through the glomerular apparatus appeared to be unchanged. In addition, the pharmacokinetic profiles of MTX also appeared not to be affected by the addition of FA. We conclude that the inhibition of reabsorption of 5-MF in the renal tube by concurrent administration of MTX and FA must be one of the causal factors for the demonstrated decrease in the plasma 5-MF levels in rats.

• 公益社団法人 日本獣医学会の論文

著者

• INOUE Keiko

  Laboratory of Cell Dynamics, Graduate School of Bioagricultural Sciences, Nagoya University

• Kokue Eiichi

  Laboratory Of Veterinary Pharmacology Department Of Veterinary Medicine Faculty Of Agriculture Tokyo

• Shimoda Minoru

  Laboratory Of Veterinary Pharmacology Department Of Veterinary Medicine Faculty Of Agriculture Tokyo

• KUDO Gen

  Laboratory of Veterinary Pharmacology, Faculty of Agriculture, Tokyo University of Agriculture and T

• SHIMODA Minoru

  Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Tokyo University of Agriculture and Technology

• KUDO Gen

  Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Tokyo University of Agriculture and Technology

• KOKUE Eiichi

  Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Tokyo University of Agriculture and Technology

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• Comparison of Dihydrofolate Reductase Activities for Folic Acid in Pigs and Rats Using In Vivo and In Vitro Evaluation Techniques
• Ameliorative Effect of Folic Acid on Pyrimethamine Teratogenesis in Pigs
• Effects of Folic Acid and Folinic Acid on Pyrimethamine Teratogenesis in Rats
• Correlation of Active Folate Availability with Effects of Folic Acid on Pyrimethamine Teratogenesis in Rats
• Effect of Folic Acid on Pharmacokinetics of Pyrimethamine in Rats
• Potentiated Decrease of Plasma Folate Levels Caused by the Coadministration of Folic Acid in Rats Treated with Methotrexate.

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