Pharmacokinetics of intravenous methotrexate in mutant nagase analbuminemic rats

Young H. Choi, Soo K. Bae, Jung M. Oh, Sun Ok Kim, Myung G. Lee

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

It has been reported that the plasma (or serum) levels of albumin and globulins were lower and higher, respectively, than the serum levels in control rats. Hence, it could be expected that these changes could affect the renal clearance (Cl,) of methotrexate in Nagase analbuminemic rats (NARs) due to changes in plasma protein binding values. Therefore, methotrexate at a dose of 100 mg/kg was administered intravenously to control rats and NARs. The plasma protein binding of methotrexate in NARs was significantly greater (29.4% increase) than the controls, probably due to the considerable binding of the drug (34.2%) to 1.8% β-plus 0.63% γ-globulins. The Clr of methotrexate in NARs was significantly slower (36.1% decrease) than the controls, due to the significantly smaller Ae0-24 h (25.8% decrease). The smaller Ae0-24 h could be due to the significantly smaller free (unbound to plasma proteins) fractions of methotrexate in plasma (13.8% decrease) in NARs, since methotrexate was mainly excreted in the urine via glomerular filtration. However, the Clnr values were comparable between the control rats and NARs. This could be because methotrexate is not metabolized considerably via hepatic CYP isozymes based on control rats pretreated with SKF 525-A (a nonspecific inhibitor of hepatic CYP isozymes in rats.

Original languageEnglish
Pages (from-to)385-392
Number of pages8
JournalBiopharmaceutics and Drug Disposition
Volume28
Issue number7
DOIs
StatePublished - Oct 2007

Keywords

  • Glomerular filtration
  • Methotrexate
  • NARs
  • Pharmacokinetics
  • Rats

Fingerprint

Dive into the research topics of 'Pharmacokinetics of intravenous methotrexate in mutant nagase analbuminemic rats'. Together they form a unique fingerprint.

Cite this