High-dose 7-hydroxymethotrexate: Acute toxicity and lethality in a rat model
Lysozyme was measured after 186 doses of methotrexate (MTX) to 88 patients. After 7.5% of the doses, lysozyme rose to between 2 and 19 micrograms/cc and in 3.2% it rose to between 20 and 120 micrograms/cc. These increases had no relationship to the age of the patients, their dose of MTX, the total number of times that MTX had been given, nor to rises in serum creatinine. It did correlate with the administration of aminoglycosides (a part of the supportive care of these patients) in two thirds of these cases. In patients who did not receive aminoglycosides, no urinary lysozyme concentration rose above 19 micrograms/cc, not even in the patients who became oliguric or required hemoperfusion. Most of these rises occurred early and were of 24 to 48 hour duration. The rises occurring after five days were persistent and were associated with prolonged MTX serum concentrations, suggesting that tubular damage due to MTX was the result of prolonged exposure to MTX, rather than the primary cause of kidney damage, i.e., the event causing the prolonged serum concentrations.