Table 6.
MBPK Model Results of the Current ATV-RTV-TFV DcNP and Comparison With Previously Reported LPV-RTV-TFV TLC-ART 101 MBPK Modeling Results
| |
Atazanavir-DcNP |
Lopinavir-DcNP (TLC-ART 101) |
||||
|---|---|---|---|---|---|---|
| Model Parameters | ATV | RTV | TFV | LPV | RTV | TFV |
| k21 (1/h) | 0.15 (0.1-0.3) | 0.40 (0.35-0.46) | 0.05 (-) | 0.03 (-) | 0.24 | 0.13 (-) |
| k31 (1/h) | 0.05 (-) | 0.05 (-) | 0.1 (-) | 0.12 | 0.19 | 0.15 (-) |
| k41 (1/h) | 0.7 (-) | 0.5 (-) | 0.15 (-) | 0.3 | 0.02 | 0.18 (-) |
| tlag1 (h) | 0.25 (-) | 0.3 (-) | 1 | 2.2 (1.1-2.9) | 2.1 (1-2.9) | 0.1 (-) |
| tlag2 (h) | 16 (9-25) | 41 (35-46) | 23 (-) | 11 (8-13) | 39 (35-44) | 24 (20-29) |
| tlag3 (h) | 440 (336-520) | 186 (169-199) | 106 (76-132) | 262 (250-281) | 182 (169-196) | 122 (119-125) |
| V5_DcNP (L/kg) | 1259a (569-1680) | 67 (22-94) | 0.7 (0.5-0.9) | 7a (6-8) | 10 (7-13) | 0.17 (0.15-0.21) |
| k75(1/h) | 0.04a (0.01-0.06) | 0.19 (0.06-0.26) | 0.026 (0.009-0.03) | 0.7a (0.6-0.9) | 0.43 (-) | 0.020 (0.018-0.03) |
| k76(1/h) | – | – | 1.7 (0.6-2.5) | – | – | 1.4 (-) |
| k78(1/h) | – | – | 0.06 (-) | – | – | 0.07 (-) |
| k87 (1/h) | – | – | 0.02 (-) | – | – | 0.03 (-) |
| V7_Free (L/kg) | 113 (97-133) | 79 (56-122) | 1.1 (0.8-1.3) | 84 (82-85) | 68 (67-69) | 1.7 (1.5-2.1) |
| K07 (1/h) | 0.29 (-) | 0.08 (0.03-0.12) | 0.4 (0.08-2) | 0.08 (0.07-0.09) | 0.10 (0.08-0.12) | 0.58 (0.56-0.62) |
Parameters according to schematic depicted in Figure 1.
DcNP containing ATV drugs scaled to equivalent DcNP containing LPV (TLC-ART 1014) drug dosages.
DcNP containing LPV (TLC-ART 101) drugs parameters values were taken from previous TLC-ART 101 MBPK study.12
k21, rate of DcNP absorption into the first delayed compartment; k31, rate of DcNP absorption into the second delayed compartment; k41, rate of DcNP absorption into the third delayed compartment; tlag1, delayed constant of delayed compartment 1; tlag2, delayed constant of delayed compartment 2; tlag3, delayed constant of delayed compartment 3; V5_DcNP, central compartmental apparent volume for DcNP; V7_Free, central compartmental apparent volume for free drug; k75, rate of degradation of DcNP into free drug between central compartments; k76, rate of absorption of free drug; k78, rate from periphery to central free compartment; k87, rate from central free compartment to periphery; k07, rate of elimination; -, not available or not applicable.
Unpaired t-test p <0.05 between nanoformulations