Premium
Pharmacokinetics of intravenous methotrexate in mutant Nagase analbuminemic rats
Author(s) -
Choi Young H.,
Bae Soo K.,
Oh Jung M.,
Kim SunOk,
Lee Myung G.
Publication year - 2007
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.565
Subject(s) - methotrexate , endocrinology , medicine , chemistry , albumin , globulin , pharmacokinetics , blood proteins , renal function , pharmacology
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 r ) of methotrexate in Nagase analbuminemic rats (NARs) due to changes in plasma protein binding values. Therefore, methotrexate at a dose of 100mg/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 Cl r of methotrexate in NARs was significantly slower (36.1% decrease) than the controls, due to the significantly smaller Ae 0–24h (25.8% decrease). The smaller Ae 0–24h 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 Cl nr 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). Copyright © 2007 John Wiley & Sons, Ltd.