Table 3.
Summary of post hoc parameter estimates from the simultaneous population pharmacokinetic artesunate-dihydroartemisinin model
| Pregnant patients | Post-partum volunteers | |||||
|---|---|---|---|---|---|---|
| Acute malaria (days 1 and 2) | Convalescent malaria (day 7) | Days 1 and 2 | Day 7 | |||
| intravenous | oral | oral | intravenous | oral | oral | |
| Artesunate | ||||||
| AUC(0,12 h) (ng ml–1 h) | 1090 (912–1180) | 138 (60.3–219) | 68.2 (32.8–130) | 1090 (1040–1130) | 77.5 (56.0–151) | 89.6 (51.4–116) |
| Cmax (ng ml–1) | 17 800 (14 800–18 100) | 140 (68.4–256) | 66.5 (24.9–151) | 17 800 (17 600–18 000) | 76.1 (42.7–160) | 74.1 (40.8–131) |
| tmax (h) | - | 1.06 (0.851–1.41) | 1.05 (0.860–1.41) | - | 1.00 (0.800–1.40) | 1.10 (0.800–1.40) |
| t1/2 (h) | 0.183 (0.121–0.776) | 0.183 (0.121–0.776) | 0.183 (0.121–0.776) | 0.240 (0.120–0.744) | 0.220 (0.120–0.744) | 0.240 (0.120–0.744) |
| CL (l h–1 kg–1) | 3.66 (3.40–3.83) | - | - | 3.69 (3.58–3.90) | - | - |
| Vd (l kg–1) | 0.231 (0.217–0.359) | - | - | 0.245 (0.217–0.3590 | - | - |
| CL/F (l h–1 kg–1) | - | 28.9 (18.1–66.3) | 59.3 (30.7–124) | - | 50.5 (26.9–69.7) | 43.3 (33.7–77.9) |
| Vd/F (l kg–1) | - | 1.81 (1.35–6.12) | 4.29 (2.38–9.12) | - | 3.17 (1.66–5.52) | 2.85 (2.03–7.74) |
| F (%) | - | 12.6 (5.46–20.6) | 6.19 (2.97–12.2) | - | 7.62 (5.25–14.0) | 8.67 (4.65–10.9) |
| Dihydroartemisinin | ||||||
| AUC(0,12 h) (ng ml–1 h) | 2250 (1860–2850) | 1580 (1310–2050) | 841 (661–1160) | 2240 (1930–2810) | 1050 (912–1510) | 1040 (912–1510) |
| Cmax (ng ml–1) | 2370 (1980–2420) | 779 (484–893) | 407 (228–507) | 2360 (2300–2450) | 549 (322–649) | 532 (322–649) |
| tmax (h) | − | 1.06 (0.851–1.41) | 1.05 (0.860–1.41) | 0.100 (0.100–0.200) | 1.00 (0.800–1.40) | 1.10 (0.800–1.40) |
| t1/2 (h) | 1.27 (1.16–1.44) | 1.27 (1.16–1.44) | 1.27 (1.16–1.44) | 1.26 (1.15–1.38) | 1.26 (1.15–1.38) | 1.26 (1.15–1.38) |
| CL (l h–1 kg–1) | 1.30 (1.04–1.59) | - | - | 1.33 (1.07–1.53) | - | - |
| Vd (l kg–1) | 1.41 (1.41–1.41) | - | - | 1.41 (1.41–1.41) | - | - |
| CL/F (l h–1 kg–1) | - | 1.89 (1.40–2.23) | 3.53 (2.48–4.47) | - | 2.71 (2.00–3.31) | 2.75 (2.00–3.31) |
| Vd/F (l kg–1) | - | 1.99 (1.90–2.28) | 3.68 (3.32–4.85) | - | 2.84 (2.61–3.56) | 2.85 (2.61–3.56) |
| F (%) | - | 71.2 (61.9–74.6) | 38.4 (29.1–42.5) | - | 49.8 (39.7–54.2) | 49.6 (39.7–54.2) |
Estimates were calculated as median values (range) from the pharmacokinetic empirical Bayes estimates in pregnant women (40–64 kg) and non-pregnant women (37–52 kg). AUC(0,12 h) area under the plasma concentration curve from 0 to 12 h after the dose, Cmax maximum plasma concentration, tmax time to reach maximum plasma concentration, t1/2 elimination half-life, CL elimination clearance after intravenous administration, Vd apparent volume of distribution after intravenous administration calculated as the sum of central and peripheral apparent volume of distribution and F oral bioavailability. After oral administration, elimination clearance and distribution volume are represented as CL/F and Vd/F.