Table 3.
Plasma Oliceridine Noncompartmental Pharmacokinetic Parameters and Summary Statistics for the Hepatic Impairment and Healthy Subjects
| Mild | Moderate | Severe | Healthy | |
|---|---|---|---|---|
| Pharmacokinetic Parameter | (N = 10) | (N = 10) | (N = 6) | (N = 8) |
| Arithmetic mean ± SD; geometric mean (%CVb) | ||||
| Cmax (ng/mL)a | 62.3 ± 48.8 | 46.6 ± 19.4 | 11.9 ± 10.6 | 54.1 ± 59.5 |
| 41.4 (78.4) | 41.9 (41.6) | 8.4 (89.5) | 34.8 (109) | |
| AUC0‐t (ng∙h/mL)a | 23.3 ± 7.9 | 29.9 ± 11.3 | 23.4 ± 10.3 | 24.1 ± 7.5 |
| 21.8 (33.8) | 28.2 (37.9) | 21.8 (44.0) | 23.3 (30.8) | |
| AUC0‐∞ (ng∙h/mL)a | 24.1 ± 8.2 | 31.2 ± 11.5 | 25.5 ± 10.6 | 24.5 ± 7.5 |
| 22.50(33.9) | 29.5 (36.9) | 23.9 (41.6) | 23.7 (30.5) | |
| CL (L/h) | 48.4 ± 23.7 | 35.7 ± 11.5 | 44.3 ± 16.2 | 43.7 ± 11.9 |
| 44.5 (48.9) | 33.9 (32.1) | 41.8 (36.5) | 42.3 (27.2) | |
| t½ (h) | 2.7 ± 0.53 | 4.7 ± 2.1 | 6.3 ± 2.6 | 2.1 ± 0.23 |
| 2.6 (20.0) | 4.3 (44.1) | 5.8 (41.2) | 2.1 (11.3) | |
| Vz (L) | 181.3 ± 81.2 | 214.6 ± 39.1 | 370.4 ± 130.3 | 129.3 ± 27.9 |
| 167.3 (44.8) | 211.5 (18.2) | 347.9 (35.2) | 126.1 (21.6) | |
| GM Ratio Mild:Healthy (90%CI) | GM Ratio Moderate:Healthy (90%CI) | GM Ratio Severe:Healthy (90%CI) | ||
| Cmax (ng/mL)a | 1.19 (0.54, 2.60) | 1.20 (0.55, 2.62) | 0.24 (0.10, 0.56) | |
| AUC0‐t (ng∙h/mL)a | 0.93 (0.68, 1.28) | 0.99 (0.71, 1.38) | 0.93 (0.66, 1.310 | |
| AUC0‐∞ (ng∙h/mL)a | 0.95 (0.70, 1.29) | 1.25 (0.92, 1.70) | 1.01 (0.72, 1.41) | |
| CL (L/h) | 1.05 (0.77, 1.43) | 0.80 (0.59, 1.09) | 0.99 (0.71, 1.38) | |
| t½ (h) | 1.26 (0.96, 1.66) | 2.09 (1.59, 2.75) | 2.79 (2.08, 3.74) | |
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; CL, total clearance; Cmax, maximum observed plasma drug concentration; %CVb, coefficient of variation between subjects; GM, geometric mean; t½, terminal elimination half‐life; Vz, volume of distribution.
a
Cmax and AUCs were dose‐normalized to a 1‐mg dose; ratio of GM determined by ANOVA.