Table 2.
Population Estimation Results for the Final Combined Pharmacokinetic-Pharmacodynamic Model.
| Parametera | Mean (%RSE)e | IIV CV%(%RSE)e | Literature values | Reference |
|---|---|---|---|---|
| CLLPVt0 (L/h) | -- | 24.0 (61.8) | ||
| CLLPVt1 | 4.73 (14.6) | -- | 3.2-5.22 | [25-29] |
| CLLPVt2 | 0.055 (34.5) | -- | NA | |
| C1 | 6.24E-04 (47.5) | 28.3 (259.) | NA | |
| VLPVt (L) | 55.7 (15.2) | 55.2 (30.7) | 42.6-61.6 | [5, 16, 25, 27] |
| KaLPVt (1/h)c | 0.325 | -- | 0.267-0.564 | [5, 26, 27] |
| Tlag,t (h)c | 0.875 (32.7) | 60.5 (63.2) | NA | |
| CLRTV (L/h) | 22.0 (11.9) | 50.5(18.3) | 8.00-24.3 | [16, 29, 33, 34] |
| Vrtv (L) | 177. (29.3) | 61.7 (41.5) | 81-275 | [33, 34] |
| KaRTV (1/h) | 0.740 (47.0) | 107. (56.6) | 0.898-1.57 | [33, 34] |
| Tlag,r (h) | 1.10d (52.3) | 69.8(64.6) | 1.05-1.96 | [33, 34] |
| fu0 | 0.00930 (4.48) | 23.4 (18.3) | NA | |
| p1 | 1.13E-05 (25.7) | 103. (31.4) | NA | |
| c (1/h) | 0.0350 | 39.3 | 0.0138 - 1.67 | [24, 35] |
| IC50 (ng/mL) | 5.84 | 53.1 | 3-7 | [6] |
| τ (h) | 3.22 | 41.6 | NA | |
| d (1/h) | 2.5E-04b | -- | 4.17E-05 - 4.17E-04 | [24, 36] |
| Δ (1/h) | 0.00288 | 61.6 | 0.00416 - 0.029 | [24, 35, 37, 38] |
| γ | 1.88 | 19.2 | NA | |
| β (mL/h/virion) | 4.79E-09 | 217. | 8.3E-10 - 1.25E-8 | [24] |
| γ (mL/h) | 75.0 | 75.3 | 5.83 - 129 | [24] |
| N (particles/h) | 19.2 | 183. | 4.17 - 292 | [39, 40] |
LPVt: total lopinavir; RTV: ritonavir; CLLPVt0: LPVt clearance; CLLPVt1: typical clearance of LPVt with median BMI (body mass index); CLLPVt2: coefficient of BMI effect.; c1: the coefficient of RTV effect; VLPVt : distribution volume of LPVt; kaLPVt: absorption rate constant of LPVt ; Tlag,t: absorption lag time of LPVt; CLRTV: clearance of RTV ;VRTV : RTV distribution volume; kaRTV: RTV absorption rate constant; Tlag,r: RTV absorption lag time; fu0: fraction of unbound drug with median α-1-acid glycoprotein [AAG (91.8 mg/dL)] , and p1 is slope for AAG; c: the clearance rate of free virions; Imax: the maximum inhibition effect of free lopinavir (LPVf); IC50: LPVf concentration at half Imax; τ mean transit time; d: the death rate of T cells; Δ death rate of infected CD4 cells; γ : hill coefficient; β infection rate; Λ: rate of new T cells are generated in the body; N: number of new virions produced by each infected CD4 cell during its lifetime.
Fixed from reference [24].
kaLPVt at and Tlag,t obtained from LPVt model with BMI as a covariate.
The maximum of Tlag,r was limited to 1.5 hours.
IIV: Inter-individual variability; CV: coefficient of variation; RSE: relative standard error.
NA. Not avaliable.