TABLE 1

Summary of published data used for the prediction of clinical drug-drug interaction for each of the tested CYP3A time-dependent inhibitors

ParameterClarithromycinMibefradilTroleandomycinVerapamilFluoxetine
Dose500 mg100 mg500 mg80 mg20–60 mg
Intervalb.i.d. (7 days)Single doseSingle doset.i.d. (2 days)q.d. (12 days)
MW747.95495.63813.97454.60309.33
Csys673 ng/ml520 ng/mla2000 ng/mlb157 ng/ml115 ng/ml
fu0.30.0050.150.10.05
Csys, u202 ng/ml2.6 ng/ml300 ng/ml15.7 ng/ml5.75 ng/ml
ReferenceGorski et al., 1998Veronese et al., 2003Kharasch et al., 2004Backman et al., 1994Lam et al., 2003
  • MW, molecular weight; Csys, systemic concentration (Cmax); fu, fraction of unbound drug [values taken from Obach et al. (2006)]; Csys, u, free systemic concentration (Cmax).

  • a Information from Welker et al. (1998).

  • b Information from the University of Washington Metabolism and Transport Drug Interaction Database (2011, http://www.druginteractioninfo.org).