Table 1

Pharmacokinetic parameters of methotrexate

ProbenecidCLtotalCLbile,pCLbile,hCLuptakefpfh
μmol/min/kg ml/min/kg
  014.7 ± 1.09.43  ± 0.3313.1  ± 0.311.9  ± 0.80.642  ± 0.0260.217  ± 0.010
  1.19.83  ± 0.195.43  ± 0.138.65  ± 0.646.75  ± 0.350.574  ± 0.0050.287  ± 0.023
  2.28.18  ± 0.934.59  ± 0.106.98  ± 0.198.12  ± 0.410.590  ± 0.0050.237  ± 0.019
  3.36.94  ± 0.152.72  ± 0.116.29  ± 0.494.82  ± 0.230.539  ± 0.0130.333  ± 0.022
  4.46.37  ± 0.812.27  ± 0.136.14  ± 0.295.10  ± 0.350.582  ± 0.0070.250  ± 0.024

Both methotrexate (0.164 μmol/min/kg) and probenecid were infused intravenously at the indicated infusion rates. The steady-state methotrexate concentration in plasma, bile, and liver were determined, and pharmacokinetic parameters (mean ± S.E. of four or five rats) were calculated.