TABLE 6

Predictions of drug interactions for mechanism-based inactivators using in vitro inactivation parameters


Inactivator

Enzyme

Affected Drug

Predicted DDI

Actual DDIa

Reference
Systemic Cmax,u
Systemic Cmax,u
Portal Cmax,u
Diltiazem CYP3A Buspirone 18 8.0 36 5.3 Lamberg et al., 1998
Erythromycin CYP3A Buspirone 52 26 48 5.9 Kivisto et al., 1997
Furafyllineb CYP1A2 Caffeine 20 20 20 ∼10 Tarrus et al., 1987
Paroxetine CYP2D6 Desipramine 6.4 4.1 6.3 5.2 Alderman et al., 1997
CYP3A Alprazolam 1.3 1.0 1.2 0.99 Calvo et al., 2004
Ritonavir CYP3A Triazolam 22 22 22 20 Greenblatt et al., 2000
Ticlopidine CYP1A2 Theophylline 4.2 1.3 2.7 1.6 Colli et al., 1987
CYP2B6 Bupropionc 20 17 20 14 Turpeinen et al., 2005
CYP2C19 Omeprazole 7.4 3.6 6.3 2.4 Tateishi et al., 1999
Tienilic acid CYP2C9 S-Warfarin 11 11 11 2.9 O'Reilly, 1982
Verapamil CYP3A Midazolam 19 6.6 22 2.9 Backman et al., 1994
Zileuton CYP1A2 Theophylline 4.3 2.1 4.6 1.9 Granneman et al., 1995
Geometric mean -fold error 2.50 1.64 2.63
Root mean squared error


15.1
7.1
19.3


  • a Clinical interaction data used in this analysis represent the largest reported interaction for each inactivator.

  • b The free fraction of furafylline in human plasma was unavailable in the scientific literature. A value of 0.39 was measured experimentally using ultrafiltration.

  • c This represents the effect on hydroxybupropion/bupropion AUC ratio, not parent exposure.