TABLE 6.
Tissue and fluid PK parameters after IM cabotegravir injection
| Geometric mean, %CVb a | Cervical tissue (n = 7) | Cervicovaginal fluid (n = 7) | Rectal tissue (n = 13) | Rectal fluid (n = 12) |
|---|---|---|---|---|
| Cmax, μg/mL b | 0.81 (105) | 0.55 (118) | 0.50 (47) | 3.27 (172) |
| Ratio to plasma Cmax (95% CI) | 0.20 (0.16–0.25) | 0.13 (0.07–0.26) | 0.10 (0.08–0.11) | 0.62 (0.31–1.25) |
| tmax, median (range), d | 7.0 (1.9–30.0) | 7.0 (1.9–84.0) | 7.0 (6.9–52.2) | 7.0 (6.9–80.0) |
| AUC0‐Wk4, μg*h/mL | 277 (104) | 203 (126) | 206 (57) | 1170 (192) |
| Ratio to plasma AUC0‐Wk4 (95% CI) | 0.16 (0.09–0.26) | 0.10 (0.04–0.25) | 0.10 (0.09–0.11) | 0.55 (0.23–1.28) |
| AUC0‐Wk8, μg*h/mL | 365 (85) | 282 (125) | 287 (39) | 1576 (203) |
| Ratio to plasma AUC0‐Wk8 (95% CI) | 0.15 (0.07–0.33) | 0.09 (0.04–0.23) | 0.11 (0.09–0.13) | 0.49 (0.21–1.11) |
| AUC0‐Wk12, μg*h/mL | 350 (79) | 381 (108) | 324 (55) | 1345 (138) |
| Ratio to plasma AUC0‐Wk12 (95% CI) | 0.12 (0.04–0.38) | 0.09 (0.02–0.33) | 0.11 (0.09–0.14) | 0.39 (0.14–1.07) |
| AUC0‐t, μg*h/mL | 523 (77) | 324 (121) | 348 (36) | 1841 (194) |
| AUC0‐∞, μg*h/mL c | 696 (NA) | 399 (100) | 292 (35) | 850 (43) |
| t1/2, d c | 15.14 (NA) | 14.83 (79) | 23.65 (23) | 12.77 (4) |
| Time > PA‐IC90, d d | 18.7 (190) | 10.8 (203) | 24.9 (75) e | 33.1 (140) f |
AUC0‐Wk4, area under the concentration–time curve from time 0 to Week 4; AUC0‐Wk8, area under the concentration–time curve from time 0 to Week 8; AUC0‐Wk12, area under the concentration–time curve from time 0 to Week 12; AUC0‐t, area under the concentration–time curve from time 0 to the last quantifiable time point; AUC0‐∞, area under the concentration–time curve from time 0 to infinity; CI, confidence interval; Cmax, maximum observed concentration; %CVb, geometric coefficient of variation; IM, intramuscular; KA, absorption rate constant; LA, long acting; NA, not available; PA‐IC90, in vitro protein‐adjusted 90% maximal inhibitory concentration; PK, pharmacokinetics; t1/2, apparent terminal phase half‐life; tmax, time to first occurrence of maximum observed concentration.
Except where noted for tmax and ratios to plasma parameters.
Lower limits of quantification were 0.025, 0.0000625 and 0.000050 μg/mL for plasma, fluids and tissues, respectively.
n = 14.
PA‐IC90 = 0.166 μg/mL.
n = 11.
n = 10.