The effect of timing of a single injection on the toxicity of methotrexate in the rat.
The possibility of a circadian rhythm in the toxicity of methotrexate was investigated in rats after a single intravenous bolus. Indices of haematological, renal and hepatic toxicity were studied, as were the pharmacokinetics of the drug. All the parameters showed a circadian variation, with maximum toxicity occurring after dosage of 06.00 h and minimum toxicity after dosage at midnight. Administration at the other two time points, 12.00 h and 18.00 h, gave intermediate results.
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001772:Blood Cell Count; D002940:Circadian Rhythm; D006207:Half-Life; D007700:Kinetics; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D013997:Time Factors; D014508:Urea / Q000097:blood
D014508:Urea; D001219:Aspartate Aminotransferases; D008727:Methotrexate