Table 5 Drug–drug interaction (DDI) studies that only report terminal volume of distribution (Vz)

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

Victim Perpetrator Victim enzymes or transporters Perpetrator enzymes or transporters Population N \(\frac{{{\text{AUC}}^{\text{DDI}} }}{{{\text{AUC}}^{\text{Con}} }}\) \(\frac{{{\text{CL}}^{\text{DDI}} }}{{{\text{CL}}^{\text{Con}} }}\) \(\frac{{V_{z}^{\text{DDI}} }}{{V_{z}^{\text{Con}} }}\) \(\frac{{{\text{MRT}}^{\text{DDI}} }}{{{\text{MRT}}^{\text{Con}} }}\) \(\frac{{t_{1/2,z}^{\text{DDI}} }}{{t_{1/2,z}^{\text{Con}} }}\) Percent AUC extrapolation Refs.
Antipyrine Cimetidine (1000 QD; 10 days) CYP1A2
CYP2C9
CYP3A4
CYP enzymes
OCT2
MATE1
Healthy subjects 7 1.41 0.79 1.24 NR 1.59 NR [40]
Desipramine Disulfiram (500 mg QD; 31 days) CYP2D6
CYP3A4
CYP2E1
CYP1A2
CYP2C9
CYP2D6
Healthy subject; male 1 1.32 0.76 0.93 NR 1.20 NR [41]
Imipramine Disulfiram (500 mg QD; 14 days) CYP2C19
CYP2D6
CYP2E1
CYP1A2
CYP2C9
CYP2D6
Healthy subjects; male 2 1.30b 0.77b 0.89b NR 1.16b NR [41]
Theophylline Cimetidine (300 mg PO QID; 1.5 days) CYP1A2
CYP3A4
CYP2E1
CYP enzymes
OCT2
MATE1
Healthy subjects; male 10 1.27c 0.79 1.00 NR 1.24 NR [42]
Theophylline Cimetidine (300 mg IV infusion QID; 1.5 days) CYP1A2
CYP3A4
CYP2E1
CYP enzymes
OCT
MATE1
Healthy subjects; male 10 1.21c 0.83 1.02 NR 1.20 NR [42]
Theophylline Cimetidine (400 mg BID; 7 days) CYP1A2
CYP3A4
CYP2E1
CYP enzymes
OCT
MATE1
Healthy subjects; male 6 1.34c 0.74 1.04 NR 1.42 NR [43]
Theophylline Cimetidine (1000 QD; 10 days) CYP1A2
CYP3A4
CYP2E1
CYP enzymes
OCT
MATE1
Healthy subjects 7 1.10 0.90 1.04 NR 1.15 NR [40]
Theophylline Ciprofloxacin (500 mg BID; 7 days) CYP1A2
CYP3A4
CYP2E1
CYP1A2
CYP3A4
Healthy subjects; male 6 1.48c 0.68 1.00 NR 1.47 NR [43]
Theophylline Ciprofloxacin (400 mg BID; 7 days) CYP1A2
CYP3A4
CYP2E1
CYP1A2
CYP3A4
Healthy subjects; male 6 1.70c 0.59 1.00 NR 1.78 NR [43]
+ Cimetidine (500 mg BID; 7 days) CYP enzymes
OCT2
MATE1
Theophylline Erythromycin (250 mg QID; 7 days) CYP1A2
CYP3A4
CYP2E1
CYP3A4
P-gp
Healthy subjects; male 8 1.38c 0.74b 0.92b NR 1.27b NR [44]
  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, CL clearance, Con control, CYP cytochrome P450, IV intravenous, MATE1 Multidrug and Toxic Extrusion 1, MRT mean residence time, NR not reported, OCT organic cation transporter, PO oral, QD once daily, QID four times a day, Refs reference, t1/2,z terminal half-life
  3. bRatios are calculated for each individual using published individual pharmacokinetic data; the reported value reflects the average of each individual ratio
  4. cAUC was calculated with the equation AUC = dose/CL using known dose and reported average values of CL