TABLE 2

Summary of kinetic indices of 6β-OHF and cortisol after coadministration of benzylpenicillin/probenecid, adefovir/probenecid, or metformin/pyrimethamine in healthy subjects

Each parameter represents the mean ± S.E.

GroupsAUC6β-OHFaX6β-OHFaCLrenal, 6β-OHFCLrenal sec, 6β-OHFbfsecc
ng • h/mlμgml/min%
Study 1d
 Control72.0 ± 7.6995 ± 108231 ± 11211 ± 1191 ± 1
 +Probenecid (750 mg)113 ± 6**917 ± 91135 ± 9**114 ± 9**50 ± 5**
Study 2e
 Control74.0 ± 6.9990 ± 130225 ± 26205 ± 2690 ± 1
 +Probenecid (750 mg)130 ± 9**1072 ± 53141 ± 12*121 ± 12*55 ± 5**
Study 3f
 Control36.2 ± 1.7480 ± 30226 ± 19206 ± 1990 ± 1
 +Pyrimethamine (50 mg)41.1 ± 4.2387 ± 42174 ± 32154 ± 3267 ± 10*
  • AUC, area under the plasma concentration-time curve from 0 to 24 hours; fsec, fraction of the tubular secretion in the net urinary excretion; X6β-OHF, cumulative amount of 6β-OHF in the urine up to 24 hours after administration of probe drug.

  • a Calculated time interval was from 0 to 12 hours.

  • b Secretion clearance of 6β-OHF in the kidney with regard to the plasma concentration using fp· glomerular filtration rate of 6β-OHF (20.4 ml/min) (Imamura et al., 2011).

  • c Fraction of 6β-OHF secreted with regard to CLrenal, 6β-OHF.

  • d Healthy subjects received an oral dose of benzylpenicillin (400,000 U) in study 1.

  • e Healthy subjects received an oral dose of adefovir (10 mg) in study 2.

  • f Healthy subjects received an oral dose of metformin (100 μg) in study 3.

  • * P < 0.05; **P < 0.01 (versus without inhibitor)