Skip to main content

Table 2 Summary of naldemedine pharmacokinetic parameters when coadministered with a P-gp inhibitor, CYP3A inhibitors, or a CYP3A inducer and when administered alone

From: Clinical Drug-Drug Interaction Studies to Evaluate the Effects of a P-Glycoprotein Inhibitor, CYP3A Inhibitors, and a CYP3A Inducer on the Pharmacokinetics of Naldemedine in Healthy Subjects

ParameterCmax (ng/mL)Tmax (h)aAUC0–last (ng·h/mL)AUC0–inf (ng·h/mL)λz (1/h)t1/2,z (h)CL/F (L/h)
P-gp inhibitor study (n = 13)
 Mean (SD)       
  Naldemedine + cyclosporine7.23 (1.84)1.00 (0.50–5.00)70.31 (12.98)70.70 (13.06)0.0786 (0.0103)8.96 (1.22)5.85 (1.16)
  Naldemedine4.90 (0.69)0.75 (0.50–1.00)39.11 (6.46)39.46 (6.52)0.0655 (0.0078)10.7 (1.4)10.4 (1.84)
 Geometric mean (CV %)       
  Naldemedine + cyclosporine7.03 (25.0) 69.17 (19.2)69.55 (19.2)0.0780 (13.3)8.89 (13.4)5.75 (19.2)
38.60 (17.2)38.94 (17.3)0.0651 (12.5)10.6 (12.6)10.3 (17.3)
  Naldemedine4.86 (14.5)
CYP3A inhibitors study (n = 14 in each cohort)
 Cohort 1
  Mean (SD)       
   Naldemedine + itraconazole4.08 (0.868)1.00 (0.50, 4.00)74.31 (22.17)82.59 (24.83)0.0317 (0.0055)22.5 (3.98)2.70 (1.12)
   Naldemedine3.77 (1.22)0.75 (0.50, 1.50)28.08 (7.300)28.31 (7.309)0.0684 (0.0173)10.7 (2.49)8.03 (4.39)
  Geometric mean (CV %)       
   Naldemedine + itraconazole4.00 (20.2) 70.88 (34.4)78.64 (35.3)0.0313 (17.8)22.2 (17.8)2.54 (35.3)
   Naldemedine3.56 (38.2)26.73 (38.2)26.98 (37.7)0.0665 (24.8)10.4 (24.8)7.41 (37.7)
 Cohort 2
  Mean (SD)       
   Naldemedine + fluconazole4.87 (0.784)1.00 (0.50, 2.50)51.00 (6.757)52.04 (6.976)0.0500 (0.0064)14.1 (1.86)3.91 (0.528)
   Naldemedine3.57 (0.874)1.00 (0.50, 3.00)27.28 (4.739)27.53 (4.772)0.0702 (0.0170)10.4 (2.44)7.45 (1.16)
  Geometric mean (CV %)      
   Naldemedine + fluconazole4.81 (16.1) 50.58 (13.3)51.60 (13.5)0.0497 (13.1)14.0 (13.1)3.88 (13.5)
   Naldemedine3.48 (23.7)26.93 (16.5)27.18 (16.5)0.0683 (24.2)10.1 (24.2)7.36 (16.5)
CYP3A inducer study (n = 14)
 Mean (SD)       
  Naldemedine + rifampin1.72 (0.370)0.51 (0.50, 1.00)3.595 (0.616)3.745 (0.613)0.2174 (0.0304)3.26 (0.55)54.7 (8.42)
  Naldemedine2.80 (0.666)1.00 (0.50, 2.50)21.84 (4.013)22.14 (4.121)0.0601 (0.0123)11.9 (1.98)9.35 (1.86)
 Geometric mean (CV %)      
  Naldemedine + rifampin1.68 (21.1) 3.549 (16.6)3.701 (16.0)0.2152 (15.5)3.22 (15.5)54.0 (16.0)
  Naldemedine2.72 (25.7) 21.49 (19.1)21.77 (19.2)0.0591 (18.5)11.7 (18.5)9.19 (19.2)
  1. AUC0–inf area under the concentration-time curve from 0 to infinity, AUC0–last area under the concentration-time curve from 0 to the last measurable concentration, CL/F apparent total clearance, Cmax maximum observed plasma concentration, CYP3A cytochrome P450 3A, CV coefficient of variation, λz apparent elimination rate constant, P-gp P-glycoprotein, SD standard deviation, t1/2,z apparent terminal elimination half-life, Tmax time to Cmax
  2. aMedian (range)