Bioavailability of methotrexate: implications for clinical use.

The absorption of oral methotrexate in syrup form has been compared in six patients with that of an identical IV dose (50 mg/m2). There was variable absorption amongst the group with respect to maximum levels achieved and the time taken to reach those levels. The area under the time-concentration curve was always smaller when the drug was given orally than after IV administration. A total of 33 patients receiving methotrexate for a variety of tumour types were followed for response to treatment and toxicity. A significantly longer methotrexate half-life (t1/2) was found in nine partial responders (9.2 +/- 1.6 h) than in the nonresponders (3.8 +/- 0.7 h). Severe methotrexate toxicity was not seen though occasional mucositis, conjunctivitis, and diarrhoea occurred in seven patients. The side effects could not be predicted from the dose, the bioavailability data, or the serum creatinine. Measurements of serum and urine methotrexate levels are useful in the assessment of absorption and bioavailability of the drug the prediction of tumour response.