Maintenance of high urinary pH is important during methotrexate treatment because:
Bladder irritation is reduced
It decreases renal tubular secretion of methotrexate
Leucovorin toxicity is increased in a dehydrated patient
Methotrexate is a weak acid
Methotrexate is a weak acid and is reabsorbed in acidic urinary pH. Higher plasma concentration may result in toxicity. Therefore, to decrease the reabsorption through renal tubules, high urinary pH must be maintained.