Table 2.
Plasma Oliceridine Noncompartmental Pharmacokinetic Parameters and Summary Statistics for the End‐Stage Renal Disease Group Versus Healthy Subjects
| ESRD (n = 8) | Healthy Subjects (n = 8) | |||||
|---|---|---|---|---|---|---|
| Pharmacokinetic Parameter | Arithmetic Mean (SD) | Geometric Mean (%CVb) | Arithmetic Mean (SD) | Geometric Mean (%CVb) | Ratio of Geometric Meansa | 90%CI for Ratio of Geometric Means |
| Cmax (ng/mL) | 9.96 (1.48)b | 9.87 (14.8)b | 8.97 (1.95) | 8.79 (22.4) | 113 | 95.4‐133.2 |
| Tmax (ng/mL)c | 0.25 (0.25‐0.25)c | 0.25 (0.25‐0.25)c | 0.25 (0.25‐0.25)c | 0.25 (0.25‐0.25)c | … | … |
| AUC0‐t (ng∙h/mL) | 19.7 (5.56)b | 19.1 (27.3)b | 18.0 (3.14) | 17.8 (17.8) | 108 | 90.1‐130.2 |
| AUC0‐∞ (ng∙h/mL) | 21.0 (5.97)b | 20.3 (28.3)b | 18.3 (3.21) | 18.1 (17.8) | 123 | 102.1‐148.4 |
| CL (L/h) | 50.8 (13.4) | 49.2 (28.3) | 56.1 (10.0) | 55.3 (17.8) | 81.2 | 67.4‐98.0 |
| t½ (h) | 3.11 (0.897) | 2.99 (31.9) | 2.44 (0.741) | 2.34 (31.9) | 128 | 95.9‐169.8 |
| Vz (L) | 219 (57.9) | 212 (27.8) | 196 (59.4) | 187 (34.5) | … | … |
AUC0‐t indicates area under the plasma concentration‐vs‐time curve from time 0 to time of last quantifiable concentration after dosing; AUC0‐∞, area under the plasma concentration‐vs‐time curve extrapolated from time 0 to infinity; BMI, body mass index; CL, total clearance; Cmax, maximum observed plasma drug concentration; %CVb, coefficient of variation between subjects; ESRD, end‐stage renal disease (chronic kidney disease stage 5 on chronic hemodialysis); t½, terminal elimination half‐life; Tmax, time to reach maximum plasma concentration; Vz, volume of distribution.
Ratio of geometric means for ESRD subjects/healthy subjects, determined by ANCOVA. The ANCOVA model includes renal function as a factor and the following covariates. AUC0‐∞ and CL: sex, age, and BMI; AUC(0‐t): sex and BMI; Cmax: BMI; t½: no covariates.
Dose‐normalized to 1 mg.
Expressed as median (min‐max).