Effect of X-irradiation on the pharmacokinetics of methotrexate in rats: alteration of the blood-brain barrier.
This study was designed to evaluate the effects of brain irradiation on the permeability of the blood-brain barrier for methotrexate (MTX). Female WAG/Rij rats were cranially irradiated with a single dose of 20 Gy of 300 kV X-rays. At different times (1-15 days) after the exposure the rats were injected intravenously with MTX (25 mg/kg body wt). Irradiation had hardly any effect on the MTX concentrations in the plasma, heart and kidneys as determined by high-performance liquid chromatography. However, irradiation resulted in a significant increase of MTX (determined by 125I-radioimmunoassay) in brain tissue per gram wet weight (187.6 +/- 17.9 pmol/g vs 46.4 +/- 29.3 pmol/g in unirradiated brain). This change in permeability of the blood-brain barrier lasted for about 9 days. The MTX elimination from the irradiated brain was the same as that from the non-irradiated brain. This indicates that only the MTX uptake and not the elimination by the brain was affected by the irradiation treatment.
D000818:Animals; D001812:Blood-Brain Barrier / Q000528:radiation effects*; D001921:Brain / Q000378:metabolism* / Q000528:radiation effects; D005260:Female; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008727:Methotrexate / Q000097:blood / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010539:Permeability; D051381:Rats; D011919:Rats, Inbred Strains
D008727:Methotrexate