TABLE 2

Application of the Yu and Tweedie and Callegari et al. approaches to trigger in vitro studies for metabolites from nine drugs in category 3

DrugMetaboliteInhibited P450AUCmetabolite/AUCparent× 100%Rmet:
Cmax,met/(Ki,parent/4)Tweedie and Yu PredictCallegari et al. Predict
AtorvastatinAtorvastatin lactoneCYP3A4890.004NoNo
2-OH-atorvastatinCYP3A41230.007YesNo
2-OH-atorvastatin lactoneCYP3A42610.01YesNo
VenlafaxineO-desmethylvenlafaxineCYP2D62860.06YesNo
BupropionHydroxybupropionCYP2D6106000.76YesYes
ThreohydrobupropionCYP2D64130.44YesYes
ErythrohydrobupropionCYP2D6720.08NoNo
AmiodaroneN-desethylamiodaroneCYP2C91500.12YesYes
GemfibrozilGemfibrozil glucuronideCYP2C8654.7NoYes
EscitalopramN-desmethylcitalopramCYP2D6360.007YesaNo
SertralineN-desmethylsertralineCYP3A4, CYP2D62590.3YesYes
CiprofloxacinOxociprofloxacinCYP1A2100.02NoNo
Capecitabine5-Deoxy-5-fluorocytidineCYP2C92840.41YesYes
5-Deoxy-5-fluorouridine2350.376YesYes
Dihydro-5-fluorouracil400.16NoYes
α-Fluoro-β-analine23601.164YesYes
  • Yes indicates in vitro P450 inhibition studies triggered by the Yu and Tweedie (2013) approach or the Callegari et al. (2013) approach. No indicates in vitro P450 inhibition studies not triggered by the Yu and Tweedie approach or the Callegari et al. approach.

  • a Covered due to the N-dealkylated metabolite (structural alert).