The effect of age on pharmacokinetics of MTX after high-dose MTX (HD-MTX) infusions was investigated. Fifty-nine patients (age: 18-83 years) received HD-MTX infusions (dosage: 1.9-3.8g/m3) for 6 hrs. All patients were divided into the following three groups according to their ages: young group (18-29 years), middle-aged group (31-57 years), and elder group (60-83 years). Mean residence time and clearance of MTX obtained by moment analysis showed a significant delay and decrease, respectively, in the elder group among patients, while there was no significance in the steady-state volume of distribution. In addition, a significantly higher concentration and slower elimination during the first 12 hr were observed in the elder group. Significant resultant decrease in renal and hepatic functions were demonstrated on days 2 and 7, respectively, indicating prompt renal damage and delayed hepatic damage in the elder patients.
These results suggest that the pharmacokinetic differences among age groups were evoked by the decreased renal function at the early stage of infusions. Furthermore, drug monitoring in the early stage following the infusion is important for preventing the onset of the severe toxicity common with HD-MTX therapy in the elder patients.
