Table 1.
PK parameters values obtained from non-compartmental modeling of LC-MS/MS data.
| Tissue type |
PK parameter | TAF+FTC NP (200 mg/kg) |
TAF+FTC solution (200 mg/kg) |
|||
|---|---|---|---|---|---|---|
| TFV | FTC | TFV | FTC | |||
| Plasma | Cmax (ng/mL) | 15954 ± 2,716# | 34026 ± 3,140# | 942 ± 137 | 850 ± 242 | |
| AUCall (Day×μg/mL) | 2.5 ± 0.4 | 3.9 ± 0.8 | 0.6 ± 0.08 | 0.2 ± 0.05 | ||
| CL (L/Day/kg) | 78.7 | 49.7 | 335.0 | 1031 | ||
| Vd (L/kg) | 145.6 | 204.3 | 285.3 | 149.3 | ||
| t1/2 (h) | 30.8 | 68.4 | 14.2 | 2.4 | ||
| MRTlast (h) | 13.5 | 13.5 | 13.4 | 5.9 | ||
| Liver | Cmax (μg/g) | 454.1 ± 15.9# | 50.2 ± 2.2# | 145.7 ± 13.2 | 1.8 ± 0.4 | |
| AUCall(Day×μg/g) | 138.7 ± 22.4 | 4.6 ± 0.2 | 92.3 ± 15.1 | 0.6 ± 0.1 | ||
| CL (g/Day/kg) | 1440 | 41709 | 2166 | 341035 | ||
| Vd (g/kg) | 5005 | 402295 | 698.4 | 287890 | ||
| MRTlast (h) | 10.6 | 10.7 | 11.1 | 12.7 | ||
| Spleen | Cmax (μg/g) | 49.1 ± 2.7# | 42.3 ± 0.8# | 3.5 ± 0.4 | 5.1 ± 1.9 | |
| AUCall(Day×μg/g) | 29.5 ± 3.0# | 6.7 ± 0.4 | 3.5 ± 0.8 | 3.4 ± 0.3 | ||
| CL (g/Day/kg) | 6709 | 28263 | 55231 | 48082 | ||
| Vd (g/kg) | 18242 | 247557 | 50110 | 71287 | ||
| MRTlast (h) | 41.1 | 27.6 | 20.7 | 18.8 | ||
| Colon | Cmax (μg/g) | 19.0 ± 1.9# | 28.2 ± 0.3# | 6.4 ± 0.9 | 2.2 ± 1.1 | |
| AUCall(Day×μg/g) | 28.7 ± 3.5# | 4.3 ± 0.6# | 7.3 ± 0.6 | 0.7 ± 0.2 | ||
| CL (g/Day/kg) | 6948 | 45284 | 25149 | 277926 | ||
| Vd (g/kg) | 50527 | 187930 | 26875 | 201348 | ||
| MRTlast (h) | 27.2 | 53.5 | 22.3 | 8.9 | ||
| Vagina | Cmax (μg/g) | 58.4 ± 23.4# | 54.1 ± 13.2# | 4.0 ± 1.1 | 4.5 ± 1.0 | |
| AUCall(Day×μg/g) | 10.9 ± 2.1 | 5.4 ± 1.1 | 2.2 ± 0.4 | 1.6 ± 0.4 | ||
| CL (g/Day/kg) | 18345 | 35791 | 92448 | 118762 | ||
| Vd (g/kg) | 46675 | 256605 | 39558 | 91640 | ||
| t1/2(h) | 42.3 | 119.3 | 6.5 | 12.8 | ||
| MRTlast (h) | 26.3 | 13.6 | 10.0 | 11.2 | ||
| Drug level (ng/G) | Day 3 | * | * | ND | 68 ± 17 | |
| Day 4 | 163.7 ± 44.9 | 19.4 ± 18.6 | * | * | ||
| Day 7 | 53.8 ± 14.0 | 90.2 ± 47.3 | * | * | ||
| Day | 11.1 ± 2.2 | ND | * | * | ||
| PBMC (active metabolites) | Cmax(pmol/106 cells) | 182 ± 60# | 182 ± 27# | 10.1 ± 9.5 | 6.2 ± 5.7 | |
| AUCall(Day×pmol) | 215.8 ± 46.7# | 88.6 ± 8.9# | 9.5 ± 2.6 | 8.7 ± 3.7 | ||
Data presented as mean ± SE; PK = Pharmacokinetic; ND=not detected; Cmax = maximum concentration; AUCall = area under the concentration-time curve; TAF= tenofovir alafenamide; TFV= tenofovir; FTC= emtricitabine; NP= nanoparticle; CL = Clearance; Vd = Volume of Distribution; MRT = Mean Residence Time;
*
indicates sample collection not scheduled for particular time point/treatment.
#
indicates p < 0.05.