Table 1.
Summary of steady-state pharmacokinetics for BUP, norBUP and NLX in the presence and absence of steady-state TPV/r
| BUP | norBUP | NLX | ||||
|---|---|---|---|---|---|---|
| PK Parameter |
BUP/NLX | BUP/NLX + TPV/r | BUP/NLX | BUP/NLX + TPV/ | BUP/NLX | BUP/NLX + TPV/r |
| AUC0–24h (h·ng/mL) | 43.9 (47.2, 20.8 – 106.9) |
43.7 (41.6, 16.4 – 112.7) |
68.7 (63.1, 33.2 – 149.5) |
14.7 (12.3, 8.8 – 31.9) |
0.35 (0.26, 0.04 – 1.51) |
0.20 (0.17, 0.04 – 1.89) |
| Mean Ratio (90% CI) |
0.99 (0.80, 1.23) 0.96 (0.76, 1.21)* |
0.21 (0.19, 0.25) 0.21 (0.18, 0.25)* |
0.56 (0.39, 0.81) 0.51 (0.36, 0.74)* |
|||
| Cmax (ng/mL) | 5.61 (5.09, 2.23 – 11.61) |
4.84 (4.94, 2.04 – 8.72) |
4.75 (4.81, 2.29 – 8.68) |
0.94 (0.96, 0.55 – 1.64) |
0.131 (0.123, 0.047 – 0.452) |
0.084 (0.085, 0.028 – 0.349) |
| Mean Ratio (90% CI) |
0.86 (0.68, 1.10) 0.86 (0.65, 1.12)* |
0.20 (0.17, 0.23) 0.20 (0.17, 0.24)* |
0.64 (0.47, 0.87) 0.63 (0.44, 0.89)* |
|||
| Cmin (ng/mL) | 1.07 (1.05, 0.35 – 3.68) |
1.00 (0.82, 0.32 – 3.56) |
2.28 (2.25, 0.74 – 5.46) |
0.46 (0.40, 0.27 – 1.05) |
0.041 (0.035, 0.027 – 0.099) |
0.033 (0.030, 0.025 – 0.090) |
| Mean Ratio (90% CI) |
0.94 (0.74, 1.19) 0.86 (0.70, 1.06)* |
0.20 (0.16, 0.25) 0.20 (0.16, 0.25)* |
NA | |||
| Tmax (h) | 0.9 (0.9, 0.5 – 2.2) |
1.3 (1.4, 0.4 – 10.2) |
1.8 (1.5, 0.8 – 10.3) |
2.0 (1.7, 0.5 – 12.2) |
1.0 (0.8, 0.5 – 5.2) |
0.8 (0.6, 0.4 – 10.2) |
| t1/2 (h) | 16.6 (15.4, 8.8 – 45.8) |
21.4 (14.5, 12.7 – 107.7) |
44.2 (30.5, 15.9 – 238.3) |
29.1 (27.3, 19.7 – 66.1) |
2.6 (2.5, 0.6 – 9.4) |
3.1 (3.3, 0.6 – 11.5) |
| CL/F (L/h) | 379 (339, 150 – 770) |
382 (386, 142 – 978) |
NA | NA | 11979 (15183, 2793 – 97912) |
21282 (23336, 3175 – 106477) |
| V (L) | 9059 (7174, 3603 – 37647) |
11787 (10430, 2610 – 60576) |
NA | NA | 46954 (36287, 12571 – 204426) |
84599 (89681, 36890 – 169342) |
PK parameter values are geometric mean (median, min-max); plasma naloxone concentrations at the end of the 24 h buprenorphine/naloxone dosing interval were not evaluated as nearly all concentrations were less than the lower limit of quantitation for the assay
The mean ratio (90% CI) represents the geometric mean ratio and 90% confidence interval of the pharmacokinetic parameter for the treatments BUP/NLX + TPV/r to BUP/NLX alone
All subjects (N = 10) received buprenorphine 16 mg/naloxone 4 mg qd, except one subject who received buprenorphine 24 mg/naloxone 6 mg qd t1/2 for NLX could not be calculated for 3 subjects with BUP/NLX and for 2 subjects with BUP/NLX+TPV/r
Cmin for BUP, norBUP was the plasma drug concentration at 24 h after dosing; for NLX, Cmin was the last measured concentration above the assay LOQ (Tlast (h): BUP/NLX 6.2 (5.6, 1.7 – 24.3); BUP/NLX+TPV/r, 4.5 (4.0, 1.4 – 24.1))
Indicates mean ratio (90% CI) for 9 subjects that received buprenorphine 16 mg/naloxone 4 mg qd.