Effect of protease inhibitors (at concentration equal to Ki) on the N-dealkylation of methadone (M) and buprenorphine (B) in 13 human liver microsomal preparations
| Concentration (μM) | Microsomal Samples | Mean | SD | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Protease Inhibitor2-a | Substrate2-a | BrM | Br21 | Br33 | Br34 | Br35 | Br36 | Br37 | Br39 | Br43 | Br48 | Br66 | Br67 | Br062 | ||
| [R] = 0.05 | [M] = 500 | 66.9 | 73.8 | 76.6 | ND | 33.0 | 51.0 | 30.4 | 26.3 | 16.7 | 27.8 | 86.7 | 34.5 | 50.7 | 47.9 | 23.2 |
| [R] = 0.05 | [B] = 100 | 35.6 | 38.4 | 90.2 | ND | 102.0 | 30.5 | 88.9 | 61.1 | 88.4 | 122.0 | 72.0 | 9.2 | 35.2 | 64.5 | 34.6 |
| [I] = 3 | [M] = 500 | 28.9 | 52.6 | 35.7 | ND | 64.4 | 32.8 | 44.6 | 43.9 | 51.0 | 60.2 | 49.7 | 39.6 | 55.2 | 46.5 | 11.0 |
| [I] = 1 | [B] = 100 | 41.4 | 55.3 | 48.0 | ND | 74.1 | 47.8 | 48.0 | 58.6 | 77.8 | 48.6 | 60.5 | 39.4 | 56.7 | 54.7 | 11.9 |
| [S] = 15 | [M] = 500 | 51.4 | 48.8 | 58.9 | ND | 79.1 | 47.9 | 40.2 | 50.6 | 66.0 | 63.6 | 54.7 | 50.6 | 61.2 | 56.1 | 10.3 |
| [S] = 7 | [B] = 100 | 74.5 | 57.4 | ND | 58.2 | 87.6 | 49.0 | 53.6 | 56.7 | 75.2 | 85.8 | 74.3 | 34.8 | 86.3 | 66.1 | 16.9 |
Results are expressed as percent of control activity, without inhibitor but with the same amount of solvent that was needed for inhibitor addition.
↵2-a R, ritonavir; S, saquinavir; I, indinavir; M, methadone; B, buprenorphine; ND, not determined. Concentrations are expressed in μmol/liter.