Table 2. Pharmacokinetic parameters for tolvaptan by CrCL group.
| Parametera | CrCL <30 ml/min (N=12) | CrCL 30–60 ml/min (N=12) | CrCL >60 ml/min (N=12) |
|---|---|---|---|
| Total tolvaptan | |||
| Cmax (ng/ml) | 535 (183) | 621 (241) | 417 (150) |
| tmax (h) | 3.5 (2.0–6.0) | 3.0 (2.0–4.0) | 2.0 (1.0–4.0) |
| AUCt (ng h/ml) | 6690 (3550) | 6470 (3090) | 3530 (1570) |
| t1/2,z (h)b | 9.1 (2.8) | 9.2 (3.3) | 10.1 (8.3) |
| AUC∞ (ng h/ml)b | 7360 (3580) | 6980 (3360) | 3890 (1910) |
| CL/F (ml/min/kg)b | 2.65 (2.40) | 2.37 (0.80) | 4.55 (2.58) |
| Unbound tolvaptan | |||
| fu (%) | 1.2 (0.8) | 0.6 (0.1) | 1.0 (0.3) |
| Cmax,u (ng/ml) | 5.89 (2.74) | 3.35 (0.85) | 4.29 (1.92) |
| AUC∞,u (ng h/ml)b | 71.8 (37.4) | 36.4 (11.9) | 37.5 (21.2) |
| CL/Fu (ml/min/kg)b | 0.034 (0.038) | 0.014 (0.006) | 0.049 (0.036) |
Abbreviations: AUCt, area under the curve from time zero to the last sampling time; AUC∞, AUC to infinity; CL/F, clearance; Cmax, maximum plasma concentration; CrCL, creatinine clearance; fu, fraction of unbound drug; tmax, time to Cmax; t1/2,z, terminal half-life; u, unbound.
a
All values are mean (±s.d.), except for tmax, which is shown as median (range).
b
n=11 per group.