Diurnal variation of methotrexate pharmacokinetics in adults with osteosarcoma

The daytime and nighttime dispositions of high dose (12 g/m2) methotrexate were examined in 8 osteosarcoma patients. The plasma and renal clearances, urine pH values and area under the curves were compared. The plasma clearance of methotrexate tended to fall after it was administered at (from 1.74±0.06 ml/min/kg to 0.47±0.01 ml/min/kg, p<0.05). Renal clearance (from 2.48±0.54 ml/min/kg to 1.18±0.3 ml/min/kg, p<0.05) and urine pH (from 7.14±0.24 to 6.16±0.26, p<0.05) decreased significantly, whereas no significant changes were observed in creatinine clearances. The area under the plotted curves increased from 220.76±28.32 to 759.71±99.56 mg/ml/min (p<0.05) after night-time exposure. These results suggest that the fall in urine pH at night results in decreased renal clearance of methotrexate.