Table 2.
Effect of Darunavir-Ritonavir on Buprenorphine and Buprenorphine Metabolite Pharmacokineticsa
| Pharmacokinetic Parameter | Before Darunavir-Ritonavir Therapy (n = 11) | During Darunavir-Ritonavir Therapy (n = 11) | P Value |
| Buprenorphine | |||
| AUC0–24, h*ng/mL | 63.3 (6.3) | 61.9 (13.8) | .90 |
| CL/F, L/h | 279 (27) | 347 (49) | .11 |
| Cmax, ng/mL | 8.4 (1.2) | 7.3 (1.5) | .31 |
| Tmax, hours, median (range) | 1.0 (0.5–1.5) | 1.0 (0.5–1.5) | NS |
| C24, ng/mL | 1.46 (0.22) | 1.72 (0.58) | .58 |
| Norbuprenorphine | |||
| AUC0–24, h*ng/mL | 85 (14.4) | 98 (14.7) | .17 |
| CL/F, L/h | 239 (33) | 222 (49) | .67 |
| Cmax, ng/mL | 5.2 (0.8) | 5.4 (0.8) | .67 |
| Tmax, hours, median (range) | 1.5 (0.5–8) | 1.5 (0.5–8) | NS |
| C24, ng/mL | 2.9 (0.5) | 3.6 (0.5) | .09 |
| Buprenorphine-3-glucuronide | |||
| AUC0–24, h*ng/mL | 36 (9.0) | 61 (14.4) | .005 |
| CL/F, L/h | 744 (157) | 419 (88) | .005 |
| Cmax, ng/mL | 5.7 (0.8) | 9.7 (1.8) | .04 |
| Tmax, hours, median (range) | 0.5 (0.5–2) | 1.0 (0.5–4) | NS |
| C24, ng/mL | 0.99 (0.34) | 1.41 (0.39) | .12 |
| Norbuprenorphine-3-glucuronide | |||
| AUC0–24, h*ng/mL | 336 (55) | 466 (25) | .29 |
| CL/F, L/h | 57 (7) | 48 (8) | .41 |
| Cmax, ng/mL | 22.5 (3.7) | 24.3 (4.8) | .73 |
| Tmax, hours, median (range) | 4 (1.5–8) | 1.0 (0.5–4) | <.02 |
| C24, ng/mL | 11.0 (1.9) | 18.2 (3.4) | .14 |
Abbreviations: AUC, area under the concentration-time curve; C24, trough plasma concentration; Cmax, maximum plasma concentration; CL/F, bioavailability-adjusted clearance; NS, not significant; Tmax, time of Cmax.
a
Data are mean (standard error) values, unless otherwise indicated. All parameter values are adjusted to a standard dose of 16 mg of buprenorphine daily. The paired t test was used to determine P values for all parameters except Tmax, for which the Wilcoxon test was used.