The complementary pharmacokinetics of artemether and lumefantrine
Pharmacokinetic parameters | ||||||||
---|---|---|---|---|---|---|---|---|
Artemether | DHA | |||||||
Subjects (n) | Food or fat content (g) | Country/Area | Cmax (ng/mL) | AUC (μg·h/mL) | t1/2 (h) | Cmax (ng/mL) | AUC (μg·h/mL) | t1/2 (h) |
Healthy volunteers (n = 14) [22] | ~65 ga | Europe | 30.8 ± 25.4 | 61.4 ± 87.5 | 2.0 ± 1.2 | 84.5 ± 26.5 | 178 ± 71 | 1.2 ± 0.4 |
Malaria patients (n = 13) [6] | 7 gd | Thailand | 34.8 | 66.4 | 1.5 | 165 | 367 | 1.3 |
Malaria patients | Local | Thailand | 66.2 ± 54.3 | 211 ± 109 | 2.2 ± 1.0 | 205 ± 102 | 604 ± 259 | 1.6 ± 0.4 |
Lumefantrine
| ||||||||
Subjects (n)
|
Food or fat content (g)
|
Country/Area
|
C
max
(μg/mL)
|
AUC
(μg·h/mL)
|
t
1/2
(day)
|
Day 7
concentration (ng/mL)
| ||
Healthy volunteers (n = 14) [22] | ~65 ga | Europe | 10.0 ± 5.5 | 383 ± 304e | 6.0 ± 1.3 | - | ||
Malaria patients (n = 266) [7] | Local standard food | Thailand | 9.0 | 561 | 3.2 | - | ||
Malaria patients (n = 74) [13] | 23 gb | Uganda | 5.6 ± 2.7 | - | - | 460 ± 288 | ||
Malaria patients (n = 17) [9] | 6.4 gc | Thailand | 7.0 | 410 | 4.1 | 350 | ||
Malaria patients (n = 13) [6] | 7 gd | Thailand | 7.34 | 252f | 2.83 | 384 |
The influence of food
Pharmacokinetics of AL in specific patient populations
Patients with renal or hepatic impairment
Paediatric patients
Pregnancy
Coartem® Dispersible
Drug-drug interactions
Concomitant medication | N | Change in exposure to artemether (AUC) | Change in exposure to DHA (AUC) | Change in exposure to lumefantrine (AUC) | Change in exposure to concomitant medication (AUC)a |
---|---|---|---|---|---|
Ketoconazole [8] | 16 | ↑ 2.4-fold | ↑ 1.7-fold | ↑ 1.7-fold | Not measured |
Mefloquine [21] | 42 | Unchanged | Unchanged | ↓ 32% | Unchanged |
Quinine [22] | 42 | ↓ 46% | ↓ 37% | Unchanged | Unchanged |
Lopinavir/ritonavir [24] | 13 | ↓ 35% | ↓ 45% | ↑ 2.4-fold | Unchanged |