Table 1.
Pharmacokinetic characteristics of Integrase Strand Transfer Inhibitors in healthy volunteers and HIV-infected persons
| BIC | CAB Oral | CAB IM | DTG | EVG | RAL | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Healthy | HIV-infected | Healthyh | HIV-infectedi | Healthyg | Healthy | HIV-infected | Healthy | HIV-infected | Healthyb | HIV-infected | HIV-infected | |
| Dose | 50mg | 50mg | 25mg | 30mg | 400mg | 50mg | 50mg | 150mga | 150mga | 400mg BID | 400mg BID | 1200mg QD |
| Cmax μg/mL) | ~8.01 | 6.15 (22.9) | 9.47 (19) | 6.37 (23) | 4.4 (31) | 6.16 (15) | 3.34 (16) | 2.66 (27.6) | 1.7 ± 0.4d | Fasted 1.20 (0.81.81)f Low 0.58 (0.39–0.88)f Mod 1.27 (0.84–1.91)f High 2.36 (1.57–3.56)f | 1.502 (135) | 6.98 (45.8) |
| Cmax (μg/mL) | 2.24 (28) | 2.61 (35.2) | 5.22 (22) | 2.85 (35) | 3.27 (27) | 1.64 (25) | 0.83 (26) | 0.490 (52.9) | 0.45 ±0.26d | Fasted 0.05 (0.03–0.08)f Low 0.42 (0.03–0.07)f Mod 0.08 (0.05–0.13)f High 0.20 (0.12–0.33)f | 0.114 (167) | 0.048 (97.5) |
| Tmax (hr) | 2.0 – 4.0 | 2.0 – 4.0 | 1.25 (0.5–4.0) | 2.5 (1.04.0) | 6.0 (1–13.1)j | 1.0 (0.5 to 2.0)f | 2.0 (0.97 to 4.0)e | 5 (5.0,5.5)d | 3 to 4 | 1.0 | 1.8 (0.5 to 4.0)e | 1.5–2.0 |
| t1/2 (hr) | 16.7 (15.8,17.1)c | 17.3 (14.8, 20.7)c | 38.8 (10) | 38.3 (57.3) | 13 to 14 | 11 to 12 | 11.0 (8.87,13.0)c | 8.62 (6.1 to 10.9)e | Distribution 1.0 Elimination 11.2 | 9 | 9 | |
| AUCτ μg*hr/mL | 89.7 (23) | 102 (26.9) | 160 (20) | 104 (28) | 2473 (26)k | 76.8 (19) | 43.4 (20) | 27.0 (29.4) | 23.0±7.5d | Fasted 4.44 (3.20–6.22)f Low 2.39 (1.72–3.33)f Mod 5.02 (3.60–7.02)f High 9.42 (6.76–13.15)f | 5.84 (99) | 24.58 (41.5) |
| Protein Binding | >99% to albumin | >99% to albumin | >99% to both albumin and alpha-1-acid glycoprotein | 99.4% albumin >> alpha-1-acid glycoprotein | 76% to 83% to Albumin | |||||||
Abbreviations: BIC, bictegravir; CAB, cabotegravir; Cmax, maximum plasma concentration; Cmin, minimum plasma concentration; DTG, dolutegravir; EVG, elvitegravir; RAL, raltegravir; Tmax, time to reach Cmax; t1/2, elimination half life; AUCτ, area under the concentration-time curve over the dosing interval
Data are presented as geometric mean (CV) unless otherwise noted.
data is with 150mg COBI.
Data are presented for fasted, low, moderate and high fat meals.
Data are presented as median (Q1,Q3).
Data are presented as mean (SD)
Data are presented as median (range).
Data are presented as GM (90% CI)
Cmin derived 4 weeks post single IM injection
Tmax data for CAB-LA are in days
AUC data for CAB-LA are 0–4 weeks.
Data are unpublished, extrapolated from Zhang et al CROI 2017, Abstract #40