Table 2.
Population pharmacokinetic parameter estimates for both lopinavir and ritonavir in final combined model
| Bootstrap |
|||
|---|---|---|---|
| Parameters | Final model estimates | Mean | 95% CIa |
| Lopinavir | |||
| CL/F, l/hb | 4.18 | 4.42 | 3.41,5.42 |
| V/F, lc | 11.6 | 11.8 | 9.20, 14.49 |
| ka, h−1 | 0.74 | 0.771 | 0.432, 1.108 |
| Sloped | 0.021 | ||
| RIF on Fe | 0.832 | ||
| Ff | |||
| Super-boosted dase | 40.5% | 45.9% | 36.3, 55.5% |
| Double dose | 22.6% | 22.5% | 14.1, 30.9% |
| IIVV, %CV | 56.6 | 54.5 | 32.1,70.2 |
| 10V ka, % CV | 76.2 | 78.7 | 37.5, 100.7 |
| 10V F, % CV | 51.8 | 50.8 | 30.9, 64.8 |
| RUV | 0.304 | 0.311 | 0.252, 0.349 |
| Ritonavir | |||
| CL/F, l/hb | |||
| No TB and after TB | 12.8 | 13.0 | 10.5, 15.5 |
| With TB | 19.1 | 18.5 | 13.9, 23.1 |
| V/F, Ic | 105 | 105 | 80.7, 129.5 |
| ka h−1 | 2.31 | 2.55 | 0.54, 4.57 |
| MTT, h | 1.28 | 1.21 | 0.80, 1.62 |
| IIV CL, % CV | 72.8 | 72.7 | 61.2, 81.6 |
| 10V CI, % CV | 41.6 | 40.0 | 21.2, 52.6 |
| IIVV, % CV | 43.3 | 42.4 | 30.3, 56.2 |
| 10V MTT, % CV | 31.1 | 46.9 | 23.6, 65.8 |
| IOV ka, % CV | 98.1 | 104.3 | 78.5, 120.3 |
| RUV | 0.339 | 0.342 | 0.291, 0.372 |
| Lopinavrr-ritonavir interactiong | |||
| Emax | 0.9 (fix) | ||
| EC50, mg/l | 0.0519 | 0.0492 | 0.0270, 0.0715 |
CI from 250 bootstraps.
(1).
(2).
Slope between ritonavir dose (mg/kg) and bioavailability of lopinavir.
The reduction of bioavailability of lopinavir caused by rifampicin (4).
Relative bioavailability of lopinavir.
(3). CI, oral clearance; CV, coefficient of variation; EC50; the ritonavir concentration needed to reach half of maximum inhibition effect on lopinavir oral clearance by ritonavir (Emax); F, bioavailability; IIV, interindividual variability; IOV, interoecasional variability; ka, oral absorption rate; MTT, mean transit time; RIF, rifampicin; RUV, residual unexplained variability; TB, antituberculosis treatment; V, volume of distribution.