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Table 2 Pharmacokinetic parameter estimates for artemether and dihydroartemisinin in different ethnic populations after artemether administration

From: Pharmacokinetics of artemether and dihydroartemisinin in healthy Pakistani male volunteers treated with artemether-lumefantrine

  Pakistani male healthy volunteers (n = 12). Oral single dose of 80 mg artemether a,b [present study] Caucasian male and female healthy volunteers (n = 16). Oral single dose of 80 mg artemether a,b[19] Thai male healthy volunteers (n = 6). Oral single dose of 200 mg artemether c[20] Malaysian male healthy volunteers (n = 6). Oral single dose of 200 mg artemether c[22] Chinese male and female patients with malaria (n = 11). Oral multiple doses of 80 mg artemether c,d[21] Chinese male and female patients with malaria (n = 11). Oral multiple doses of 80 mg artemether a,c,d[21]
Artemether       
CMAX (ng/mL) 184 ± 100 104 ± 40 118 (112-127) 310 ± 150 157 ± 93 e 133 ± 49 e
TMAX (hr) 1.56 ± 0.68 2.00 (1.00-4.00) 3.00 (1.00-10.0) 1.88 ± 0.21 1.73 ± 0.46 e 2.13 ± 0.49 e
CL/F (L/hr) 257 ± 140 - - 365 ± 190 - -
V/F (L) 666 ± 220 - - 988 ± 520 543 ± 950 e 189 ± 130 e
T1/2 (hr) 2.00 ± 0.71 1.90 ± 0.80 3.10 (1.00-9.60) 2.00 ± 0.59 1.16 ± 0.44 0.860 ± 0.26
TLAG (hr) 0.130 ± 0.23 - - 0.330 ± 0.13 0.480 ± 0.24 e 0.830 ± 0.37 e
AUC0-∞/dose (hr × ng/mL/mg) 4.82 ± 2.2 4.00 ± 1.7 5.50 (1.65-22.2) 3.36 ± 1.4 5.73 ± 3.1 6.36 ± 2.5
AUC0-∞ (hr × ng/mL) 385 ± 170 320 ± 140 1100 (330-4440) 671 ± 270 1830 ± 1000 2040 ± 800
Dihydro-artemisinin       
CMAX (ng/mL) 126 ± 46 104 ± 45 379 (162-702) 273 ± 64 161 ± 63 e 105 ± 42 e
TMAX (hr) 1.69 ± 0.59 2.50 (1.00-4.00) 6.00 (2.00-12.0) 1.92 ± 0.13 1.86 ± 0.45 e 2.44 ± 0.44 e
CL/F (L/hr) 269 ± 57 - - - - -
V/F (L) 702 ± 220 - - - 275 ± 230 e 246 ± 99 e
T1/2 (hr) 1.80 ± 0.31 2.10 ± 0.90 10.6 (4.70-19.2) - 0.950 ± 0.42 1.06 ± 0.25
TLAG (hr) 0.250 ± 0.24 - - 0.290 ± 0.10 0.350 ± 0.28 e 0.820 ± 0.54 e
AUC0-∞/dose (hr × ng/mL/mg) 3.86 ± 0.76 4.33 ± 1.5 34.5 (4.35-202) 3.94 ± 1.2 9.14 ± 2.0 9.80 ± 4.5
AUC0-∞ (hr × ng/mL) 294 ± 58 331 ± 110 6590 (830-38700) 753 ± 230 2930 ± 640 3140 ± 1400
  1. a Fixed oral combination of 80 mg artemether and 120 mg lumefantrine
  2. b administered together with a high-fat meal
  3. c administered on an empty stomach
  4. d administered at 0, 8, 24 and 48 hours
  5. e pharmacokinetic parameter estimates based on the first dose
  6. Values are reported as mean ± SD or as median (range).
  7. Dose normalized exposures were calculated using the published mean or median value for total exposure divided with the mean or median dose.
  8. CMAX = maximum observed plasma drug concentration, TMAX = observed time to reach CMAX, CL/F = oral clearance, V/F = apparent oral volume of distribution, T1/2 = terminal elimination half-life, TLAG = absorption lag time, and AUC0-∞ = area under the plasma concentration time curve after the first dose to infinity.