Enhanced systemic availability of methotrexate in the presence of morin in rats

Soon Sun Hong, Ming Ji Jin, Hyo Kyung Han

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The present study aimed to investigate the effect of morin on the pharmacokinetics of methotrexate (MTX) in rats. Pharmacokinetic parameters of MTX were determined in rats following an intravenous administration of MTX (2mg/kg) in the presence and absence of morin (25 mg/kg, p.o.). The cellular accumulation of MTX was also examined by using MDCK cells stably overexpressing hOAT1 or hOAT3. Compared with the control given MTX alone, pretreatment with morin 15 min prior to MTX administration significantly altered the pharmacokinetics of MTX in rats. Renal clearance and total clearance of MTX were reduced by 42% and 58%, respectively, in the presence of morin. Accordingly, the systemic exposure of MTX in the rats pretreated with morin was significantly higher than that from the control group. The mean residence time (MRT) and terminal plasma half-life of MTX were prolonged by 3.3- and 2.4-fold, respectively, by the concurrent use of morin. The cellular uptake of MTX (20 μM) was significantly reduced by the coincubation with morin (100 μM) in MDCK-hOAT1 cells but not in MDCK-hOAT3 cells. Taken together, morin appeared to be effective in altering the pharmacokinetics of MTX in rats, likely by the inhibition of OAT1-mediated renal excretion.

Original languageEnglish
Pages (from-to)189-193
Number of pages5
JournalBiopharmaceutics and Drug Disposition
Volume29
Issue number4
DOIs
StatePublished - May 2008

Keywords

  • Morin
  • MTX
  • Pharmacokinetics
  • Rats
  • Renal excretion

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