Table 6 Intravenous pharmacogenomic interaction studies and disease state drug–drug interaction studies

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

Drug Enzyme Population N \(\frac{{{\text{AUC}}^{\text{Int}} }}{{{\text{AUC}}^{\text{Con}} }}\) \(\frac{{{\text{CL}}^{\text{Int}} }}{{{\text{CL}}^{\text{Con}} }}\) \(\frac{{V_{\text{ss}}^{\text{Int}} }}{{V_{\text{ss}}^{\text{Con}} }}\) \(\frac{{{\text{MRT}}^{\text{Int}} }}{{{\text{MRT}}^{\text{Con}} }}\) \(\frac{{t_{1/2,z}^{\text{Int}} }}{{t_{1/2,z}^{\text{Con}} }}\) Percent AUC extrapolation Refs.
Metoprolol CYP2D6 Control: healthy subjects, white, male, CYP2D6 extensive metabolizers; 58–80 kg 3 2.56c 0.40 0.51 1.29e 1.81a 34%/15%a [15]
Phenotype: healthy subjects, white, male, CYP2D6 poor metabolizers; 65–86 kg 4
Midazolam CYP3A Control: healthy subjects, African American, CYP3A5*1/*1; 57–97 kg for all subjects 6 0.98 1.04 0.79a 0.70a 0.93 8%/14%a [21]
Phenotype: healthy subjects, African American, CYP3A5*1/*X; 57–97 kg for all subjects 7
Midazolam CYP3A Control: healthy subjects, African American, CYP3A5*1/*1; 57–97 kg for all subjects 6 1.05 0.99 0.72a 0.70a 0.96 8%/14%a [21]
Phenotype: healthy subjects, African American, CYP3A5*1/*X; 57–97 kg for all subjects 6
Theophylline CYP1A2
CYP3A4
CYP2E1
Control: healthy subjects; average weight 80.7 kg 9 1.54c 0.65 0.70g 1.2g 1.76 8%/14%a [28]
Disease state: patients with liver cirrhosis; average weight 68.6 kg 9
  1. Pharmacokinetic values reported in the table are based on published average values, unless otherwise noted
  2. AUC area under the curve, CL clearance, Con control (indicating the wild-type pharmacogenomic phenotype or healthy subject group), CYP cytochrome P450, Int interaction (indicating the reduced function pharmacogenomic phenotype or disease state group); MRT mean residence time, Refs reference, t1/2,z terminal half-life, 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. cAUC was calculated with the equation AUC = dose/CL using known dose and reported average values of CL
  5. eMRT was calculated with the equation Vss = CL·MRT using reported average values of CL and Vss
  6. gRatios are calculated by digitization of a published plasma concentration–time profile of a single representative subject (one healthy subject and one patient with liver cirrhosis), which may not be reflective of all subjects in the study