Park J M, Moon C H, Lee M G
College of Medicine, Ajou University, Suwon, Korea.
Res Commun Mol Pathol Pharmacol. 1996 Sep;93(3):343-52.
The pharmacokinetic changes of methotrexate (MTX) were investigated after 1-min intravenous (iv) administration of MTX, 8 mg/kg, to the control and the streptozotocin-induced diabetes mellitus (SIDM) rats. After 1-min iv infusion of MTX, plasma concentrations of MTX declined polyexponentially for both groups of rats. In the SIDM rats, the plasma concentrations of MTX were significantly lower up to 5 min, however, significantly higher from 60 min than those in the control rats. In the SIDM rats, the volume of distribution at steady state was significantly higher (1010 versus 265 ml/kg) than that in the control rats, and this was due to the significantly increased unbound fraction of MTX (73.0 versus 58.1%) in serum of SIDM rats. This resulted in a significantly increased mean residence time (53.2 versus 13.8 min) in the SIDM rats. All 12 control rats survived until sacrificed (24 hr), however, 6 out of 15 SIDM rats died within 6 h after iv administration of MTX, suggesting that the iv doses of MTX in diabetes mellitus patients may need to be modified if the present rat data could be extrapolated to human beings.
