Table 5.
Rifabutin and 25-O-desacetyl-rifabutin pharmacokinetics when coadministered with lersivirine (study 2)
| Effect studied and parameter (units) | Treatment 1 (n = 17)a |
Treatment 2 (n = 17)b |
Ratio of adjusted geometric means (A/B) | 90% CI | ||
|---|---|---|---|---|---|---|
| Geometric mean (% CV) | Adjusted geometric mean (A)c | Geometric mean (% CV) | Adjusted geometric mean (B) | |||
| Effect of lersivirine on PKs of rifabutin | ||||||
| AUC24 (ng · h/ml) | 5,146 (19) | 5,103 | 5,030 (18) | 5,010 | 1.02 | 0.96, 1.08 |
| Cmax (ng/ml) | 578 (33) | 572 | 522 (31) | 519 | 1.10 | 0.98, 1.24 |
| C24 (ng/ml) | 78.7 (26) | 78.0 | 78.9 (28) | 78.3 | 1.00 | 0.94, 1.06 |
| Tmax (h)d | 4 (1–8) | 4 (2–6) | ||||
| Effect of lersivirine on PKs of 25-O-desacetyl-rifabutin | ||||||
| AUC24 (ng · h/ml) | 203 (39) | 202 | 275 (40) | 275 | 0.73 | 0.68, 0.79 |
| Cmax (ng/ml) | 21.3 (41) | 21.0 | 28.9 (43) | 28.7 | 0.73 | 0.66, 0.81 |
| C24 (ng/ml) | 3.04 (37) | 3.04 | 3.60 (46) | 3.59 | 0.85 | 0.73, 0.98 |
| Tmax (h)d | 4 (1–8) | 4 (2–6) | ||||
a
Treatment was with lersivirine at 1,000 mg q.d. plus rifabutin at 300 mg q.d. One subject discontinued.
b
Treatment was with rifabutin at 300 mg q.d. One subject discontinued.
c
The adjusted geometric mean was obtained by exponentiation of the mean estimate from the statistical analysis. Natural log-transformed data were analyzed using a mixed-effect model with sequence, period, and treatment as fixed effects and subject within sequence as a random effect.
d
Data represent median (range).