TABLE 2

List of drug–drug interactions analyzed in this study

Initial parameter settings and the results of the analyses are summarized in the corresponding figures and tables.

SubstratesMetabolitesInhibitorsPutative Enzyme(s) InvolvedAUCRID NumberAdditional DataaObjective FunctionReference (PubMed ID)
ParentMetabolite
Chlorpromazine7-Hydroxy chlorpromazineQuinidine (166 mg)CYP2D6, CYP3A1.401Table S7, Fig. S7AUCinfAUCinf8739822
Desipramine2-Hydroxy desipramineFluoxetine (60 mg)CYP2D62.58b2Table S8.1, Fig. S8.1AUCinfAe1544284
10.6c3Table S8.2, Fig. S8.2
FentanylNorfentanylFluconazole (200 mg)CYP3A1.264Table S9.1, Fig. S9.1AUCinfAUCinf17987285
Voriconazole (200 mg)CYP3A1.395Table S9.2, Fig. S9.2
Flurbiprofen4ʹ-Hydroxy flurbiprofenFluconazole (200 mg)CYP2C91.756Fig. 2/Table S.10.1, Fig. S10.1AUCAUC22943633
2.027Table S10.2, Fig. S10.223047652
HydrocodoneHydromorphoneQuinidine (83 mg)CYP2D61.218Table S11, Fig. S11AUCinfAUCinf7693389
Imipramine2-Hydroxy imipramine, desipramineFluoxetine (60 mg)CYP2D6, CYP2C19, CYP3A2.08b9Table S12.1, Fig. S12.1AUCinfAUCinf/Ae1544284
3.56c10Table S12.2, Fig. S12.2
Lansoprazole5-Hydroxy lansoprazole, lansoprazole sulfoneFluvoxamine (25 mg)CYP2C194.00d11Table S13.1, Fig. S13.1AUCinfAUCinf15496639
2.50e12Table S13.2, Fig S13.2
Clarithromycin (400 mg)CYP3A1.38d13Table S13.3, Fig. S13.315752376
1.76e14Table S13.4, Fig. S13.4
1.81f15Table S13.5, Fig. S13.5
LosartanEXP-3174Fluconazole (200 mg)CYP2C9, CYP3A1.6916Table S14.1, Fig. S14.1AUCinfAUCinf9357393
1.2717Table S14.2, Fig. S14.29551703
Omeprazole5-Hydroxy omeprazole, omeprazole sulfoneFluvoxamine (25 mg)CYP2C195.62d18Table S15.1, Fig. S15.1AUCinfAUC/AUCinf15025747
2.38e19Table S15.2, Fig. S15.2
OxycodoneNoroxycodone, oxymorphoneQuinidine (166 mg)CYP2D61.1320Table S16.1, Fig. S16.1AUCinfAUC/AUCinf9871425
Voriconazole (200 mg)CYP3A3.5721Table S16.2, Fig. S16.218836708
Itraconazole (200 mg)CYP3A2.4322Table S16.3, Fig. S16.320076952
Paroxetine (20 mg)CYP2D61.1123Table S16.4, Fig. S16.420642550
Ropivacaine(S)-2ʹ,6ʹ-pipecoloxylidideItraconazole (200 mg)CYP3A1.2324Table S17, Fig. S17AUCinfAUC11322176
  • AUC, area under the plasma concentration–time curve; AUCinf, AUC from time 0 to infinity.

  • a Tables and figures indicated with an S are found in the supplemental data.

  • b Fluoxetine single dose.

  • c Fluoxetine multiple dose.

  • d CYP2C19 extensive metabolizer (EM).

  • e CYP2C19 intermediate metabolizer (IM).

  • f CYP2C19 poor metabolizer (PM).