Table 1.
Pharmacokinetic parameters of dolutegravir in blood plasma, cervicovaginal fluid, cervical tissue, and vaginal tissue
| Blood Plasma | PK1 (first dose) Median (IQR) | PK2 (steady state) Median (IQR) | Accumulation ratio Median (IQR) |
| AUC0-24h(ng*h/mL) | 38,300 (31,600–45,400) | 55,400 (43,300–62,200) | 1.42 (1.28–1.50) |
| Clast (ng/mL) | 821 (610–956) | 120 (102–149) | - |
| Cmax (ng/mL) | 3,000 (2,380–3,470) | 3,770 (3,430–5,250) | - |
| Tmax (h) | 2.0 (1.0–4.8) | 2.5 (1.3–4.0) | - |
| t½ (h) | Not calculated* | 14.8 (13.6–16.1) | - |
| Cervicovaginal Fluid | PK1 (first dose) Median (IQR) | PK2 (steady state) (Median (IQR) | Accumulation ratio Median (IQR) |
| AUC0-24h (ng*h/mL) | 2,600 (1,280–8,100) | 3,160 (2,820–5,220) | 0.82 (0.71–1.12) |
| Clast (ng/mL) | 93.1 (41.2–122) | 8.7 (6.6–10.2) | - |
| Cmax (ng/mL) | 149 (84.4–435) | 230 (93.4–347) | - |
| Tmax (h) | 9.9 (5.7–17.9) | 7.9 (3.7–11.9) | - |
| t½ (h) | Not calculated* | 13.5 (11.1–14.9) | - |
| Cervical Tissue | PK1 (first dose) Median (IQR) | PK2 (steady state) Median (IQR) | Accumulation ratio (AUC0-24 PK2/AUC0-24 PK1) |
| AUC10–24h (ng*h/g) | 2,750 | 5,300 | 1.93 |
| Clast (ng/g) | 59.6 (41.6–77.5) | 149 (114–183) | - |
| Cmax (ng/ g) | 236 (148–324) | 395 (232–557) | - |
| Tmax (h) | 6 | 6 | - |
| t½ (h) | Not calculated* | Not calculated* | - |
| Vaginal Tissue | PK1 (first dose) Median (IQR) | PK2 (steady state) Median (IQR) | Accumulation ratio (AUC0-24 PK2/AUC0-24 PK1) |
| AUC0-24h (ng*h/g) | 2,730 | 4,740 | 1.74 |
| Clast (ng/ g) | 52.1 (16.0–88.1) | 77.8 (51.1–105) | - |
| Cmax (ng/ g) | 399 (392–407) | 405 (337–472) | - |
| Tmax (h) | 6 | 6 | - |
| t½ (h) | Not calculated* | Not calculated* | - |
Clast is C24h for PK1 and C72h for PK2
Tissue AUCs are composite geometric means of all subjects
*
t½ was not calculated for blood plasma or cervicovaginal fluid after the first dose because there was not a clear elimination phase in all subjects by 24 hours and was not calculated for cervical or vaginal tissue at either time point because each individual subject only had one sampling time and concentrations remained high at 24 hours.