List of compounds with corresponding in vitro induction data and published clinical data used to generate RIS
Drug | Dosea | Total Cmaxa | Free Cmaxa | EC50b | Emaxb (Fold-Induction) | RIS | Clinical DDI (Decrease in AUC of Coadministered Drug) | References for Clinical DDI Data | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Midazolam | Ethinylestradiol | |||||||||
| mg | μM | % | ||||||||
| Carbamazepine | 400-800 | 34 | 8.5 (fu = 0.25)c | 62 | 2.5 | 0.30 | 94 | 41 | Backman et al., 1996b; Crawford et al., 1990 | |
| Nifedipine | 30-60 | 0.29 | 0.014 (fu = 0.05) | 17 | 8.3 | 0.0068 | Lack of clinical induction with other P450 substrates | Horsmans et al., 1991; Sachse et al., 1998 | ||
| Phenobarbital | 75 | 52 | 26 (fu = 0.50) | 222 | 5.5 | 0.58 | N.A. | 70 | Back et al., 1980 | |
| Phenytoin | 200-300 | 70 | 5.2 (fu = 0.075) | 44 | 5.2 | 0.55 | N.A. | 50 | Crawford et al., 1990 | |
| Pioglitazone | 15-45 | 2.8 | 0.028 (fu < 0.01) | 4.6 | 4.1 | 0.025 | 26 | 11 | Pioglitazone product label | |
| Rifampicin | 300-600 | 10 | 2.5 (fu = 0.25) | 1.9 | 13 | 7.4 | 95 | 64 | Backman et al., 1996a; LeBel et al., 1998 | |
| Rosiglitazone | 8 | 1.4 | 0.0028 (fu = 0.002) | 14.5 | 2.9 | 0.00056 | No effect on ethinylestradiol or nifedipine PK | Harris et al., 1999; Inglis et al., 2001 | ||
| Troglitazoned | 600 | 6.3 | 0.063 (fu = 0.01) | 3.0 | 2.4 | 0.049 | N.A. | 30 | Loi et al., 1999 | |
| Compound A | 40 | 0.028 | 0.0028 (fu = 0.1) | 1.3 | 4.8 | 0.010 | 39 | N.A. | McRobie et al., 2004 | |
| Compound A | 120 | 0.106 | 0.011 (fu = 0.1) | 1.3 | 4.8 | 0.039 | 62 | N.A. |
| |
N.A., no data available; PK, pharmacokinetics.
↵ a Dosage and plasma concentration information obtained from product labels and/or cited DDI studies.
↵ b EC50 and Emax parameters generated by curve-fitting of Fa2N-4 cell data, with the exception of troglitazone.
↵ c fu = unbound fraction in plasma.
↵ d Concentration-response curves for troglitazone were limited by toxicity at higher concentrations; therefore, Emax was estimated as the highest fold-induction at a non-toxic concentration, and EC50 the concentration producing half-maximal fold-induction.