Table 1

Comparison of observed in vivo metabolic clearances of tolbutamide with predicted values from human liver microsomal data reported in the literature

In Vitro DataIn Vivo Data
IndividualKm1-aVmax1-aCLint1-bCLint1-cCLh1-d (Predicted)Reference1-eIndividualCLmet1-f(Actual)
μM pmol/min/mg μl/min/mg ml/min/kg ml/min/kg ml/min/kg
1953143.302.970.0891210.19
2811712.111.900.0571220.15
3811591.961.770.0531230.14
42051600.780.700.0212240.13
5843694.393.950.1182250.14
61102171.971.770.0532260.14
71523001.971.780.0533270.14
81632601.591.440.0433280.17
9971151.191.070.0323290.16
101321310.990.890.0274300.17
111211401.161.040.0314
122021770.880.790.0244
133484191.201.080.0325
141334343.262.940.0885
151373872.822.540.0765
161202241.871.680.0506
171762131.211.090.0336
18623936.345.700.1706
19882743.112.800.0846
201232922.372.140.0646
Mean1352572.222.000.0591-g 0.15
S.D.641021.371.230.0370.019
  • 1-a  Individual apparentKm and Vmax values for tolbutamide hydroxylation from separate literature reports.

  • 1-b  In vitro CLint calculated using Vmax/Km.

  • 1-c  Predicted in vivo CLint.

  • 1-d  Hepatic clearance predicted using the well-stirred model.

  • 1-e  The number refers to separate literature reports: 1, Doecke et al., 1991; 2,Hemeryck et al., 1999; 3, Shin et al., 1999; 4, Komatsu et al., 2000a; 5,Hickman et al., 1998; 6, Miners et al., 1988.

  • 1-f  In vivo CLmet of tolbutamide hydroxylation observed in human subjects (Data fromGross et al., 1999).

  • 1-g  P < 0.0001 compared with the observed in vivo CLmet of tolbutamide using a ttest. See Experimental Procedures for details.