Table 6.
Drug interaction studies between artemether-lumefantrine and lopinavir/ritonavir, showing median lumefantrine, artemether and dihydroartemisinin pharmacokinetic parameters with and without lopinavir/ritonavir
| Study (Reference) | Population | Comparator groups | Artemether- lumefantrine dose | Concomitant fat intake | Samples per participant (matrix) | Lumefantrine | Artemether | Dihydro-artemisinin | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AUC | Cmax | Day 7 | AUC | Cmax | AUC | Cmax | ||||||
| Kredo | HIV infected, malaria negative adults | Parallel: Lopinavir based ART vs. ARV-naïve | Single dose (Phase 1) | Yes | 22 (Plasma) | Single dose: AUC(0-inf) 1852 vs. 1133 μg.h/mL | 5.26 vs. 2.50 μg/mL | NA | NA | NA | NA | NA |
| Standard 6-dose regimen (Phase 2) | Yes | 33 (Plasma) | AUC(0-inf) 2477 vs. 445 μg.h/mL | 28.15 vs 8.76 μg/mL | 3170 vs. 336 ng/mL | AUC(0-8h) 220 vs. 151 ng.h/mL | 85.8 vs. 59.7 ng/mL | AUC(0-8h) 283.6 vs. 123.8 ng.h/mL | 77.5 vs. 42.2 ng/mL | |||
| Byakika-Kibwika25 | HIV infected, malaria negative adults | Parallel: Lopinavir based ART vs. ARV- naïve | Single dose | Yes | 9 (Plasma) | AUC(0-inf) 267 vs. 47 μg.h/mL | 7.10 vs. 2.53 μg/mL | NA | AUC(0-inf) 162 vs 271 ng.h/mL | 56 vs 112 ng/mL | AUC(0-inf) 180 vs 217 ng.h/mL | 73 vs 66 ng/mL |
| German29 | Healthy adult volunteers | Cross-over: Artemether lumefantrine given before and after 26 days Lopinavir-based ART | Standard 6 dose regimen | Yes | 10 (Plasma) | AUC(0–264) 1073 vs 456 | 17.4 vs 12.5 μg/mL | NA | AUC(0-inf) 40.5 vs. 62.0 ng.h/mL | 11.2 vs 14.3 ng/mL | AUC(0-inf) 109 vs 198 ng.h/mL | 37.3 vs 58.8 ng/mL |
| Achan35 | HIV-infected children with malaria on ART | Parallel: Lopinavir-based ART vs. NRTI-based antiretrovirals | Standard 6 dose regimen | Not reported | 1 (Capillary blood) | NA | NA | Lopinavir: 926 ng/mL | NA | NA | NA | NA |
| Nevirapine: 388 ng/mL | ||||||||||||
| Efavirenz: 97 ng/mL | ||||||||||||