Table 7 Utilization of the Sodhi and Benet methodology [3] to discriminate clearance (CL) from bioavailability (F) changes for orally dosed midazolam (victim) and clarithromycin (perpetrator) from the study of Quinney et al. [17]

From: Volume of Distribution is Unaffected by Metabolic Drug–Drug Interactions

Victim Perpetrator \(\frac{{{\text{AUC}}^{\text{DDI}} }}{{{\text{AUC}}^{\text{Control}} }}\) Percent AUC extrapolation (DDI/control) \(\frac{{V_{\text{ss}} /F^{\text{DDI}} }}{{V_{\text{ss}} /F^{\text{Control}} }}\) \(\frac{{V_{\text{ss}}^{\text{DDI}} }}{{V_{\text{ss}}^{\text{Control}} }}\) \(\frac{{F^{\text{DDI}} }}{{F^{\text{Control}} }}\) \(\frac{{{\text{CL}}/F^{\text{DDI}} }}{{{\text{CL}}/F^{\text{Control}} }}\) \(\frac{{{\text{CL}}^{\text{DDI}} }}{{{\text{CL}}^{\text{Control}} }}\) Refs.
Midazolam (IV) Clarithromycin (500 mg BID; 7 days) Observed: 3.2 Observed: 44%/19%a Observed: 1.16a Observed: 2.12 Observed: 0.35 [17]
15N3-Midazolam (oral) Clarithromycin (500 mg BID; 7 days) Observed: 8.2 Observed: 33%/12%a Observed: 0.35a Assumed: 1 Estimated: 2.84b Observed: 0.14 Estimated: 0.40b [17]
  1. Pharmacokinetic values reported in the table are based on published average values, unless otherwise noted
  2. AUC area under the curve, BID twice daily, DDI drug–drug interaction, IV intravenous, Refs reference, Vss volume of distribution at steady state
  3. aRatios are calculated by digitization of published average plasma concentration–time profiles and performing a non-compartmental analysis
  4. bRatios are calculated for each individual using published individual pharmacokinetic data; the reported value reflects the average of each individual ratio