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]

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]

Pharmacokinetic values reported in the table are based on published average values, unless otherwise noted

AUC area under the curve, BID twice daily, DDI drug–drug interaction, IV intravenous, Refs reference, V_ss volume of distribution at steady state

^aRatios are calculated by digitization of published average plasma concentration–time profiles and performing a non-compartmental analysis

^bRatios are calculated for each individual using published individual pharmacokinetic data; the reported value reflects the average of each individual ratio