Table 2.
Population pharmacokinetic parameter estimates based on the final model simultaneously fitting both lopinavir and ritonavir
| Lopinavir | Ritonavir | |||
|---|---|---|---|---|
| Parameters | Estimates | 95% CI* | Estimates | 95% CI* |
| CL/F (l h−1)† | 37.9 | 28.5, 52.1 | 19.2 | 18.4, 22.2 |
| RIF on CL/F (+)‡ | 71.0% | 65.7%, 75.4% | 36.0% | 35.2% , 40.0% |
| Vc/F (l) | 54.7 | 50.5, 64.7 | 22.6 | 21.9, 24.6 |
| ka (h−1) | 0.991 | 0.63, 1.43 | 3.28 | 2.90, 3.38 |
| Relative bioavailability when given with RIF | 0.80 | 0.76, 0.85 | 0.55 | 0.54, 0.59 |
| Residual variability (proportional %) | 12.7 | 11.6, 13.6 | 18.8 | 17.1, 20.3 |
| Evening effect on bioavailability (+)‡ | 42.0% | 38.0%, 48.2% | 45.0% | 41.4%, 53.6% |
| Evening effect on CL/F (–)‡ | 32.7% | 29.6%, 38.4% | 32.7% | 29.6%, 38.4% |
| Bioavailability/10 mg ritonavir(+)c | 8.1% | 5.7%, 11.2% | ||
| Intercompartmental clearance (Q/F) (l h−1) | 31.0 | 25.7, 34.7 | ||
| Vp/F (l) | 56.6 | 50.8, 66.0 | ||
| NN | 2.03 | 1.83, 2.37 | ||
| MTT (h) | 1.44 | 1.39, 1.53 | ||
| IIV CL/F (%CV) | 20.2 | 12.7, 25.1 | 21.5 | 11.5, 31.7 |
| IIV V/F (%CV) | 27.2 | 10.3, 41.4 | 10.2 | 9.85, 10.5 |
| IOV F (%CV) | 21.9 | 17.1, 24.0 | 30.3 | 24.1, 40.7 |
| IOV ka (%CV) | 94.2 | 46.5, 150.1 | ||
| IOV CL/F (%CV) | 11.8 | 4.55, 16.1 | 20.4 | 15.5, 25.1 |
| IOV RUV (%CV) | 17.1 | 9.63, 25.2 | ||
| IIV F (%CV) | 30.3 | 17.4, 49.6 | ||
| IOV MTT (%CV) | 27.9 | 19.6–38.2 | ||
| Lopinavir-ritonavir interaction | Estimates | 95% CI* |
|---|---|---|
| Emax | 95.3% | 94.5%, 96.3% |
| EC50 (mg l−1) | 0.0351 | 0.0194, 0.0438 |
CI confidence intervals based on mean and SD from 10 bootstrap samples.
CL/F of lopinavir without ritonavir;
(+) the effect is increased (–) the effect is decreased;
increase in bioavailability per every 10 mg ritonavir dose. CL central clearance, Vc,central volume of distribution, Vp peripheral volume of distribution, F bioavailability, ka absorption rate, RIF rifampicin, NN number of transit compartment, MTT mean transit time, IIV interindividual variability, IOV interoccasion variability, RUV residual unexplained variability, Emax the maximum inhibition effect of ritonavir on lopinavir, EC50 is the ritonavir concentration required to reach half of Emax.