TABLE 2

Clinical probe substrates used in GSK clinical DDI studies, and assumptions of fm and Fg used for DDI predictions

Clinical ProbefmFg
CYP1A2Caffeine0.95a1
Theophylline0.8a1
CYP2C8Cerivastatin0.82b,i1
CYP2C9Flurbiprofen0.45c1
Warfarin0.91a1
CYP2D6Desipramine0.9a1
Dextromethorphan0.97d1
CYP3A4Midazolam0.89h0.57e
Atorvastatin0.68b0.35f
Nifedipine0.78b0.74e
Simvastatin0.92a0.29g
Triazolam0.95a0.64e
  • fm, fraction of available dose metabolized by hepatic P450; Fg, fraction of absorbed dose escaping gut metabolism by CYP3A4 (assumed to be 1 for all other P450s).

  • a Venkatakrishnan, et al., 2007;

  • b Ohno et al., 2007;

  • c Greenblatt, et al., 2006;

  • d Borges, et al., 2005;

  • e Obach, et al., 2006;

  • f Lilja, et al., 1999;

  • g Lilja, et al., 2004;

  • h Chen, et al., 2006;

  • i Wang, et al., 2002.