TABLE 1.
Pharmacokinetic parameter estimates for artemether, dihydroartemisinin, and lumefantrine, with or without nevirapine-based antiretroviral therapy
| Pharmacokinetic parametera | Control group (n = 16) | Nevirapine-based ART group (n = 11) | Nevirapine-based ART control group | Pb |
|---|---|---|---|---|
| Artemether | ||||
| Cmax (GM [95% CI]) (ng/ml) | 19.1 (13.2–27.5) | 6.04 (4.07–8.97) | 0.32 | <0.01 |
| Tmax (median [IQR]) (h) | 1.0 (0.50–1.0) | 1.5 (0.50–3.0) | 1.5 | 0.12 |
| AUC0–6 (GM [95% CI]) (h · ng/ml) | 63.0 (47.4–83.6) (n = 13) | 19.9 (13.8–28.7) (n = 10) | 0.32 | <0.01 |
| AUC0–∞ (GM [95% CI]) (h · ng/ml) | 93.2 (66.3–131) (n = 12) | 30.8 (14.7–64.5) (n = 6) | 0.33 | <0.01 |
| t1/2 (median [IQR]) (h) | 3.9 (2.1–5.9) (n = 12) | 2.2 (1.2–4.5) (n = 6) | 0.56 | 0.16 |
| Dihydroartemesinin | ||||
| Cmax (GM [95% CI]) (ng/ml) | 61.4 (47.7–78.9) | 47.3 (35.5–63.1) | 0.77 | 0.37 |
| Tmax (median [IQR]) (h) | 1.0 (1.0–2.0) | 1.5 (1.0–3.0) | 1.5 | 0.54 |
| AUC0–6 (GM [95% CI]) (h · ng/ml) | 160 (129–198) | 143 (115–179) | 0.89 | 0.69 |
| AUC0–∞ (GM [95% CI]) (h · ng/ml) | 189 (151–237) | 193 (152–244) | 1.02 | 0.84 |
| t1/2 (median [IQR]) (h) | 1.9 (1.5–3.7) | 2.6 (2.0–3.8) | 1.37 | 0.37 |
| Lumefantrine | ||||
| Cmax (GM [95% CI]) (μg/ml) | 11.0 (8.0–15.0) | 5.81 (3.50–9.65) | 0.53 | 0.07 |
| Tmax (median [IQR]) (h) | 2.0 (2.0–6.0) | 2.0 (0.0–6.0) | 1.0 | |
| AUC0–96 (GM [95% CI]) (h · μg/ml) | 295 (208–419) | 151 (98–232) | 0.51 | 0.048 |
| AUC0–∞ (GM [95% CI]) (h · μg/ml)c | 426 (298–609) | 180 (117–278) | 0.42 | 0.02 |
| t1/2 (median [IQR]) (h) | 116 (80.4–153) | 39.2 (35.9–50.2) | 0.34 | <0.01 |
The maximal plasma concentration (Cmax) and the time to Cmax (Tmax) were estimated by visual inspection, whereas the area under the concentration-time curve (AUC) and the elimination half-life (t1/2) were determined by noncompartmental analysis. Unless noted otherwise, the n value used to calculate each pharmacokinetic measure was that for the full study group, as indicated in the column heading. GM, geometric mean; CI, confidence interval; IQR, interquartile range.
The Mann-Whitney U test was used to evaluate differences in pharmacokinetic parameters between groups. A P value of <0.05 was considered significant.
The AUC0–∞ values include residual area from the previous dose, due to the long elimination half-life of lumefantrine.