Background
Sources of variation introduced by study methodology
Artesunate and DHA protein binding
Intravenous administration: artesunate pharmacokinetics
Ref. | Subjects & Regimen | Cmax (ng/mL) | Clearance (L/kg/hr) | Volume (L/kg) | Half-life (min) | AUC (ng*hr/mL) |
---|---|---|---|---|---|---|
[7] Batty, Le et al, 1998 | 12 Vietnamese adults with vivax malaria 120 mg IV AS over 2 min | 13685†a | 3.01 | 0.16 | 2.19 | 876† |
[9] Binh et al, 2001 | 17 healthy Vietnamese volunteers; subjects randomized into two groups, both receiving: 120 mg IV AS over 2 min | 3.0; 2.2 | 0.19; 0.16 | 2.6; 3.3 | 846; 1269† | |
[10] Ilett et al, 2002 | 23 Vietnamese adults with uncomplicated falciparum malaria; subjects randomized into two groups, both receiving: 120 mg IV AS over 2 min | 16146; 16530† | 2.8; 2.1 | 0.22 | 3.2 | 1038; 1230† |
[11] Li et al, 2009 | 30 healthy volunteers 0.5, 1, 2, 4, or 8 mg/kg IV AS over 2 min | 4797; 6128; 19420; 36100; 83340 | 1.3; 18; 1.3; 1.4; 1.6† | Vss: 0.092; 0.187; 0.106; 0.109; 0.165† | 7.2; 8.4; 14.4; 9.0; 12.6† | 386; 593; 1595; 3038; 6994† |
[12] Nealon et al, 2002 | 28 paediatric Gabonese patients with severe malaria randomized into two groups Group 1: 2.4 mg/kg IV AS Group 2: 1.2 mg/kg IV AS | Group 1: 29677a Group 2: 15369a | Group 1: 3.12†a Group 2: 4.26†a | Group 1 Vss: 0.17†a Group 2 Vss: 0.44†a | Group 1: 1.5a Group 2:11.5a | Group 1: 1042†a Group 2: 555†a |
[13] Newton et al, 2006 | 17 adults with severe falciparum malaria in Thailand 2.4 mg/kg IV AS over 2 min [2.1 (1.4 - 2.8 mg/kg)] | 130+†a | 64a | Vss: 15.2a | 13.2+†a | 49.2†a |
[8] Batty. Thu et al, 1998 | 26 adult uncomplicated falciparum malaria patients in Vietnam 120 mg IV AS over 2 min | 2.33a | 0.140a | 2.73 | 1146† | |
[14] Davis et al, 2001 | 30 parasitaemic adults with falciparum malaria Group 1: 12 with complications (120 mg IV AS over 2 min) Group 2: 8 without complications (120 mg IV AS over 2 min) Group 3: 10 with moderately severe complications (240 mg IV AS infused over 4 hours; samples taken after infusion discontinued) | Group 1: 1.63 Group 2: 2.49 Group 3: 3.07 | Group 1: 0.08 Group 2: 0.24 Group 3: 0.23 | Group 1: 2.3 Group 2: 4.3 Group 3: 3.2 |
Ref. | Subjects & Regimen | Cmax (ng/mL) | Tmax (min) | Clearance (L/kg/hr) | Volume (L/kg) | Half-life (min) | AUC (ng*hr/mL) |
---|---|---|---|---|---|---|---|
[7] Batty, Le et al, 1998 | 12 Vietnamese adults with vivax malaria 120 mg IV AS over 2 min | 2192†a | 8a | 1.10 | 0.92 | 36.7 | 1845† |
[9] Binh et al, 2001 | 17 healthy Vietnamese volunteers; subjects randomized into two groups, both receiving: 120 mg IV AS over 2 min | 1507; 1678† | 9; 16 | 53; 47 | |||
[10] Ilett et al, 2002 | 23 Vietnamese adults with uncomplicated falciparum malaria; subjects randomized into two groups, both receiving: 120 mg IV AS over 2 min | 2758; 2730†a | 7; 9a | 0.64; 0.48 | 0.8; 0.55 | 59; 50 | 2872; 3298† |
[11] Li et al, 2009 | 30 healthy volunteers 0.5, 1, 2, 4, or 8 mg/kg IV AS over 2 min | 428; 802; 1286; 3148; 4744 | 9.6; 15; 9.6; 7.2; 24† | 1.3; 0.98; 1.1; 0.86; 0.82† | Vss: 1.734; 2.201; 1.860; 1.701; 2.403† | 57.6; 92.4; 69.0; 82.2; 128.4† | 385; 1082; 1850; 4886; 10410 |
[12] Nealon et al, 2002 | 28 paediatric Gabonese patients with severe malaria randomized into two groups Group 1: 2.4 mg/kg IV AS Group 2: 1.2 mg/kg IV AS | Group 1: 3011†a Group 2: 1584†a | Group 1: 0.5a Group 2: 1.4a | Group 1: 2.16†a Group 2: 1.08†a | Group 1 Vss: 0.75a Group 2 Vss: 0.77a | Group 1: 20.7a Group 2: 32.0a | Group 1: 923†a Group 2: 737†a |
[13] Newton et al, 2006 | 17 adults with severe falciparum malaria in Thailand 2.4 mg/kg IV AS over 2 min [2.1 (1.4 - 2.8 mg/kg)] | 605†a | Tmax reached by 15 min | 5.6a | Vss: 1.9a | 20.4†a | 418†a |
[8] Batty. Thu et al, 1998 | 26 adult uncomplicated falciparum malaria patients in Vietnam 120 mg IV AS over 2 min | 2648†a | 9.0a | 0.75a | 0.76 | 40.2 | 2377† |
[14] Davis et al, 2001 | 30 parasitaemic adults with falciparum malaria Group 1: 12 with complications Group 2: 8 without complications Group 1 & 2: 120 mg IV AS over 2 min Group 3: 10 with moderately severe complications (240 mg IV AS infused over 4 hours; samples taken after infusion discontinued) | Group 1: 2417† Group 2: 2531† Group 3: 910 † | Group 1: 10.4 Group 2: 9.9 Group 3: 240 (end of infusion) | Group 1: 1.09 Group 2: 0.73 Group 3: 0.73 | Group 1: 0.77 Group 2: 1.01 Group 3: 0.78 | Group 1: 40.0 Group 2: 64.1 Group 3: 46.2 | Group 1: 2078† Group 2: 2559† Group 3: 5573† |
Krishna et al, 2001 [15] | 34 Ghanaian children (8 months - 7 years) with moderate falciparum malaria Group 1 & 2: AS rectal suppository, IV AS 2.4 mg/kg 12 hr later Group 3: 2.4 mg/kg IV AS, AS rectal suppository 12 hr later | Groups 1 & 2: 1280†a Group 3: 1592 †a | Groups 1 & 2: 12†a Group 3: 12† | Groups 1 & 2: 1.5a Group 3: 1.0a | Groups 1 & 2: 0.6a Group 3: 0.9a | Groups 1 & 2: 18†a Group 3: 31.8†a | Groups 1 & 2: 1166†a Group 3: 1706†a |
Intravenous administration: DHA pharmacokinetics
Intravenous administration: bioassay results
Intramuscular administration: artesunate and DHA pharmacokinetics
Ref. | Subjects & Regimen | Cmax (ng/mL) | Tmax (min) | Clearance (L/kg/hr) | Volume (L/kg) | Half-life (min) | AUC (ng*hr/mL) |
---|---|---|---|---|---|---|---|
[10] Ilett et al, 2002 | 11 Vietnamese adults with uncomplicated falciparum malaria 120 mg AS administered by intramuscular injection | 884†a | 12a | 2.9 | 2.6 | 41 | 999† |
[21] Hien et al, 2004 | 9 Vietnamese adults with severe falciparum malaria 2.4 mg/kg AS administered by intramuscular injection | 2195†a | 2.84a | 1.09a | 30a | 856†a | |
[12] Nealon et al, 2002 | 28 paediatric Gabonese patients with severe malaria randomized into two groups Group 1: 2.4 mg/kg IV AS, followed by 1.2 mg/kg IM AS 12 hours later Group 2: 2.4 mg/kg IM AS, followed by 1.2 mg/kg IV AS 12 hours later | Group 1: 615†a Group 2: 661†a | Group 1: 7.2a Group 2: 8.0a | Group 1: 2.4†a Group 2: 3.48†a | Group 1 Vss/F: 2.07a Group 2 Vss/F: 3.98a | Group 1: 25.2a Group 2: 48.2a | Group 1: 535†a Group 2: 544†a |
Ref. | Subjects & Regimen | Cmax (ng/mL) | Tmax (min) | Clearance (L/kg/hr) | Volume (L/kg) | Half-life (min) | AUC (ng*hr/mL) |
---|---|---|---|---|---|---|---|
[10] Ilett et al, 2002 | 11 Vietnamese adults with uncomplicated falciparum malaria 120 mg AS administered by intramuscular injection | 1166†a | 45a | 0.73 | 1.1 | 64 | 2474† F: 88% |
[21] Hien et al, 2004 | 9 Vietnamese adults with severe falciparum malaria 2.4 mg/kg AS administered by intramuscular injection | 870†a | 35a | 1.18a | 1.79a | 52.7a | 1496†a |
[12] Nealon et al, 2002 | 28 paediatric Gabonese patients with severe malaria randomized into two groups Group 1: 2.4 mg/kg IV AS, followed by 1.2 mg/kg IM AS 12 hours later Group 2: 2.4 mg/kg IM AS, followed by 1.2 mg/kg IV AS 12 hours later | Group 1: 341a Group 2: 626a | Group 1: 25.9a Group 2: 40.5a | Group 1: 2.16†a Group 2: 1.5†a | Group 1: Vc/F: 1.2a Vss/F: 1.32a Group 2: Vc/F: 1.2a Vss/F: 1.28a | Group 1: 31.9a Group 2: 40.2a | Group 1: 396†a Group 2: 1123†a Combined group F: 86.37%a |
Oral administration: artesunate pharmacokinetics
Ref. | Subjects | Regimen | Tmax (hours) |
---|---|---|---|
[23] | 15 healthy Cambodian male adults | 4 mg/kg AS once with mefloquine | 0.75a |
[6] | 8 healthy adults in Australia | 150 mg AS once | 0.65 (n = 6)a |
[24] | 20 healthy adult males in Australia | 200 mg/day × 3 days alone (Period 1); repeated with mefloquine after washout (Period 2) | Period 1/Day 1: 0.6b Period 1/Day 3: 0.6b Period 2/Day1: 0.5b Period 2/Day 3: 0.6b |
[25] | 6 healthy adults in Geneva | 200 mg AS once | 0.25 (5/6 subjects) 0.5 (1/6 subjects) |
[26] | 23 healthy Malaysian adults | 200 mg AS once with amodiaquine as fixed or non-fixed product | Fixed:0.26 Non-fixed:0.53 |
[27] | 13 healthy adults in Africa | Mean dose: 4.26 mg/kg with (ACT) or without (AS only) amodiaquine as single dose | AS only: 0.62 ACT: 0.86 |
[28] | 8 healthy male Thai adults | 300 mg AS (Guilin or Arenco formulation) | Guilin: 0.25a Arenco: 0.31a |
[29] | 10 healthy male Vietnamese adults | 200 mg AS once daily × 5 days | Day 1: 0.8a Day 5: 0.8a |
[30] | 12 healthy male Malaysian adults | 200 mg AS once | 0.66 ± 0.34 |
[31] | 11 male Thai adults with uncomplicated falciparum malaria | 200 mg AS once, followed by 100 mg 12 hours later, then 100 mg once daily for another 4 days | Acute: 0.5a Convalescence:1.0a |
[32] | 43 adults with uncomplicated falciparum malaria in Thailand | AS+mefloquine as fixed (200 mg AS) or nonfixed (4 mg/kg AS) combination | Fixed:0.833 (n = 19) Nonfixed:0.925 (n = 23) |
[33] | 13 male and female adult patients in the DRC with acute uncomplicated falciparum malaria | 200 mg AS once daily × 3 days with amodiaquine | 1.4 (n = 10) |
[34] | 86 acute uncomplicated falciparum malaria patients from Malawi and Gambia | 1, 2, or 4 mg/kg AS with chlorproguanil and dapsone once daily × 3 days | 1 mg/kg: 1.08a 2 mg/kg: 0.55a 4 mg/kg: 1.03a |
[35] | 6 male Thai adults with uncomplicated falciparum malaria and 6 healthy male adults | 100 mg AS once | Healthy: 0.71 Patients: not determined |
[36] | 57 children (2-14 years) with uncomplicated falciparum malaria in Gabon | AS dose (mg/kg/day) with pyronaridine Group A:2.1(1.4-2.4) Group B:3.3(2.4 - 3.9) Group C:4.8(3.0 - 6.1) Group D: 3.8(3.0-4.3) | Group A:0.6 Group B:0.7 Group C:1.0 Group D:0.5 |
[37] | 40 children and adults with uncomplicated falciparum malaria in Pailin, Cambodia and 40 adults with uncomplicated falciparum malaria in Wang Pha, Thailand | At each site: Group 1: AS monotherapy: 2 mg/kg/day × 7 days Group 2: AS 4 mg/kg/day × 3 days + mefloquine | Thailand: Group 1: 0.38a Group 2: 0.50a Cambodia: Group 1:0.50a Group 2: 1.00a |
Ref. | Subjects | Artesunate regimen | Artesunate half-life (hours) |
---|---|---|---|
[29] | 10 healthy male Vietnamese adults | 200 mg once daily × 5 days | Day 1: 0.43a Day 5: 0.50a |
[30] | 12 healthy male Malaysian adults | 200 mg single dose | 0.49 |
[28] | 8 healthy male Thai adults | 300 mg AS (Guilin or Arenco formulation) | Guilin:0.53 Arenco:0.57 |
[26] | 23 healthy Malaysian adults | 200 mg AS + amodiaquine as fixed or non-fixed product | Fixed:0.63 Non-fixed:0.76 |
[34] | 86 acute uncomplicated falciparum malaria patients from Malawi and Gambia | 1, 2, or 4 mg/kg AS + chlorproguanil and dapsone once daily × 3 days | 1 mg/kg: 0.515b 2 mg/kg: 0.478b 4 mg/kg: 0.467b |
[31] | 11 male Thai adults with uncomplicated falciparum malaria | 200 mg AS once, followed by 100 mg 12 hours later, then 100 mg once daily × 4 days | Acute: 0.36a Convalescence: 0.54a |
[35] | 6 male Thai adults with uncomplicated falciparum malaria and 6 healthy male adults | 100 mg AS once | Healthy: 0.41 Patients: not determined |
[36] | 57 children (2-14 years) with uncomplicated falciparum malaria in Gabon | AS dose (mg/kg) with pyronaridine Group A:2.1(1.4-2.4) Group B:3.3(2.4 - 3.9) Group C:4.8(3.0 - 6.1) Group D: 3.8(3.0-4.3) | Group A: 0.8 (n = 12) Group B:1.1 (n = 12) Group C:0.5 (n = 10) Group D:1.2 (n = 13) |
[37] | 40 children and adults with uncomplicated falciparum malaria in Pailin, Cambodia and 40 adults with uncomplicated falciparum malaria in Wang Pha, Thailand | At each site: Group 1: AS monotherapy: 2 mg/kg/day × 7 days Group 2: AS 4 mg/kg/day × 3 days + mefloquine | Thailand: Group 1: 0.37a Group 2: 0.58a Cambodia: Group 1: 0.29a Group 2: 0.29a |
Oral administration: DHA pharmacokinetics
Ref. | Subjects | Oral AS regimen | AUC (ng*hr/mL) | Cmax (ng/mL) |
---|---|---|---|---|
[29] | 10 healthy male Vietnamese adults | 200 mg once daily × 5 days | ASa Day 1: 67 Day 5: 60 | ASa Day 1:67 Day 5: 58 |
DHAa Day 1:1158 Day 5:1300 | DHA Pooled:654 | |||
[30] | 12 healthy male Malaysian adults | 200 mg AS once | AS 119 | AS 256.3 |
DHA AUC0-t:1331 | DHA 873.7 | |||
[27] | 13 healthy adults in Africa | Mean dose: 4.26 mg/kg with (ACT) or without (AS only) amodiaquine single dose | AS AS only: 206.4 ACT: 183.3 | AS AS only: 231.8 ACT: 141.6 |
DHA AS only: 2044.4 ACT: 1410.5 | DHA AS only: 844.5 ACT: 446.2 | |||
[28] | 8 healthy male Thai adults | 300 mg AS (Guilin and Arenco formulations) | AS Guilin: 406 Arenco: 190.8 | AS Guilin: 397 Arenco: 194 |
DHA Guilin: 1630 Arenco: 2600 | DHA Guilin: 500 Arenco:928 | |||
[6] | 8 healthy adults in Australia | 150 mg once | AS AUC0-6 hr:154 (n = 6) | ASa 111 (n = 6) |
DHA AUC0-6 hr: 824 | DHAa 546 | |||
[26] | 23 healthy Malaysian adults | 200 mg once with amodiaquine as fixed or non-fixed product | AS† Fixed: 391.1 Non-fixed: 213.2 | AS† Fixed: 333 Non-fixed: 444 |
DHA† Fixed: 1468.9 Non-fixed: 1656.0 | DHA† Fixed: 609.8 Non-fixed:874.5 | |||
[34] | 86 acute uncomplicated falciparum malaria patients from Malawi and Gambia | 1, 2, or 4 mg/kg AS with chlorproguanil and dapsone once daily × 3 days | ASb 1 mg/kg: 64.6 (n = 16) 2 mg/kg:151(n = 19) 4 mg/kg: 400(n = 23) | ASb 1 mg/kg: 48.9 2 mg/kg: 106 4 mg/kg: 224 |
DHAb 1 mg/kg: 538 (n = 24) 2 mg/kg: 1445(n = 29) 4 mg/kg: 383(n = 23) | DHAb 1 mg/kg: 228 2 mg/kg: 581 4 mg/kg: 1414 | |||
[39] | 21 children (5 - 13 years) with uncomplicated malaria in Uganda | 4 mg/kg once daily with amodiaquine × 3 days | AS 113 (data pooled from all subjects) | AS 51 (data pooled from all subjects) |
DHAa 1404 | DHAa 473 | |||
[32] | 43 adults with uncomplicated falciparum malaria in Thailand | 200 mg/day for fixed dose AS-mefloquine tablet (n = 20) or 4 mg/kg/day as nonfixed (n = 23) AS-mefloquine | AS AUC0-t: Fixed:310 (n = 19) Nonfixed: 419 (n = 21) | AS Fixed:255 (n = 19) Nonfixed:451 (n = 23) |
DHA AUC0-t: Fixed:3027 Nonfixed: 3633 | DHA Fixed:1234 Nonfixed:2043 | |||
[35] | 6 male Thai adults with uncomplicated falciparum malaria and 6 healthy male adults | 100 mg AS once | AS AUC0-12 hr Healthy: 97 Patients: not determined | AS Healthy: 114 Patients: not determined |
DHA AUC0-12 hr Healthy: 501 Patients: 1144 | DHA Healthy: 339 Patients: 554 | |||
[36] | 57 children (2-14 years) with uncomplicated falciparum malaria in Gabon | AS dose (mg/kg) Group A:2.1(1.4-2.4) Group B:3.3(2.4 - 3.9) Group C:4.8(3.0 - 6.1) Group D: 3.8(3.0-4.3) | AS Group A: 104 (n = 12) Group B: 154 (n = 12) Group C:232 (n = 10) Group D: 179 (n = 13) | AS Group A: 93 Group B:154 Group C: 287 Group D: 171 |
Administered with pyronaridine | DHA Group A: 1055 Group B: 1989 Group C: 2961 Group D: 2245 | DHA Group A:479 Group B: 940 Group C:1186 Group D:792 | ||
[37] | 40 children and adults with uncomplicated falciparum malaria in Pailin, Cambodia and 40 adults with uncomplicated falciparum malaria in Wang Pha, Thailand | At each site: Group 1: AS monotherapy: 2 mg/kg/day × 7 days Group 2: AS 4 mg/kg/day × 3 days + mefloquine | AS†a AUC0-24 hr Thailand: Group 1: 128 Group 2: 237 Cambodia: Group 1: 173 Group 2: 338 | AS†a Thailand: Group 1: 171 Group 2: 200 Cambodia: Group 1: 270 Group 2: 316 |
DHA†a AUC0-24 hr Thailand: Group 1: 1308 Group 2: 2957 Cambodia: Group 1: 1382 Group 2: 4123 | DHA†a Thailand: Group 1: 859 Group 2: 1191 Cambodia: Group 1: 802 Group 2: 1590 |
Ref. | Subjects | Artesunate regimen | DHA half-life (hours) |
---|---|---|---|
[29] | 10 healthy male Vietnamese adults | 200 mg once daily × 5 days | 0.87 (from pooled data) |
[30] | 12 healthy male Malaysian adults | 200 mg single dose | 0.49 |
[40] | 20 male and female healthy Thai adults | 4 mg/kg once | 0.74a |
[27] | 13 healthy adults in Africa | Mean dose: 4.26 mg/kg with (ACT) or without (AS only) amodiaquine single dose | AS only:1.46 ACT: 3.08 |
[28] | 8 healthy male Thai adults | 300 mg AS (Guilin or Arenco formulation) | Guilin: 1.77 Arenco:1.73 |
[41] | 10 healthy Vietnamese males | 100 mg AS once | Half-life: 0.55b |
[25] | 6 healthy adults in Geneva | 200 mg AS once | 0.65 |
[26] | 23 healthy Malaysian adults | 200 mg once with amodiaquine as fixed or non-fixed product | Fixed:1.68 Non-fixed:1.42 |
[24] | 20 healthy adult males in Australia | 200 mg/day × 3 days alone (Period 1); repeated with mefloquine after washout (Period 2) | Period 1/Day 1: 1.14 Period 1/Day 3: 1.14 Period 2/Day 1: 1.02 Period 2/Day 3: 1.09 |
[23] | 15 healthy Cambodian male adults | 4 mg/kg once with mefloquine | 1.30b |
[42] | 12 healthy adults | 200 mg once | 0.68 |
[34] | 86 acute uncomplicated falciparum malaria patients from Malawi and Gambia | 1, 2, or 4 mg/kg AS with chlorproguanil and dapsone once daily × 3 days | 1 mg/kg: 0.779b 2 mg/kg: 0.917b 4 mg/kg: 1.09b |
[7] | 12 Vietnamese adult male vivax malaria patients | 100 mg single dose | 0.67 (n = 11) |
[8] | 26 Vietnamese adult patients with uncomplicated falciparum malaria | 100 mg single dose | 0.66 (n = 16) |
[39] | 21 children (5 - 13 years) with uncomplicated malaria in Uganda | 4 mg/kg once daily with amodiaquine × 3 days | 1.3a |
[38] | 24 children with uncomplicated falciparum malaria in Gabon | 4 mg/kg once daily for 3 days in one of two formulations (blister pack and fixed dose) of AS/mefloquine | Fixed dose: 0.9(n = 9)a Blister pack: 1.0 (n = 11)a |
[32] | 43 adults with uncomplicated falciparum malaria in Thailand | 200 mg/day for fixed dose AS-mefloquine tablet or 4 mg/kg/day as nonfixed AS-mefloquine | Fixed: 1.1 (n = 14) Nonfixed: 0.8 (n = 18) |
[31] | 11 male Thai adults with uncomplicated falciparum malaria | 200 mg AS once, followed by 100 mg 12 hours later, then 100 mg once daily × 4 days | Acute: 0.64a Convalescence: 0.66a |
[43] | 24 pregnant Karen women in the 2nd and 3rd trimesters with uncomplicated falciparum malaria | 4 mg/kg once daily × 3 days with atovaquone plus proguanil | Half-life: 1.0 (n = 13)a PopPK half-life estimate: 1.81 hr |
[35] | 6 male Thai adults with uncomplicated falciparum malaria and 6 healthy male adults | 100 mg AS once | Healthy: 0.85 Patients: 1.06 |
[9] | 8 Vietnamese adults with uncomplicated falciparum malaria and 10 healthy Vietnamese adults | 150 mg once | Healthy: 0.77 Patients: 0.88 |
[53] | 26 2nd and 3rd trimester pregnant women with asymptomatic falciparum parasitaemia, the same women postpartum, and 25 non-pregnant asymptomatic, parasitaemic controls | 200 mg once | Pregnant: 1.28a Postpartum:1.63a Controls: 1.41a |
[36] | 57 children (2-14 years) with uncomplicated falciparum malaria in Gabon | AS dose (mg/kg) Group A:2.1(1.4-2.4) Group B:3.3(2.4 - 3.9) Group C:4.8(3.0 - 6.1) Group D: 3.8(3.0-4.3) Administered with pyronaridine | Group A:1.0 Group B: 0.9 Group C: 1.2 Group D:1.2 |
[37] | 40 children and adults with uncomplicated falciparum malaria in Pailin, Cambodia and 40 adults with uncomplicated falciparum malaria in Wang Pha, Thailand | At each site: Group 1: AS monotherapy: 2 mg/kg/day × 7 days Group 2: AS 4 mg/kg/day × 3 days + mefloquine | Thailand: Group 1: 0.71a Group 2: 0.85a Cambodia: Group 1: 0.84a Group 2: 0.77a |
Oral administration: bioassay results
Oral administration: population pharmacokinetic analyses
Rectal administration: AS and DHA pharmacokinetics
Ref. | Subjects & Regimen | Cmax (ng/mL) | Tmax (hours) | Half-life (hours) | AUC (ng*hr/mL) |
---|---|---|---|---|---|
[49] Sirivichay et al, 2007 | 16 paediatric patients with uncomplicated falciparum malaria 10 mg/kg (n = 7) or 20 mg/kg (n = 9) AS as rectal suppositories | 507; 561†a | 0.8; 1.0a | 0.9; 0.9a | 692; 1076†a |
[50] Halpaap et al, 1998 | 12 paediatric patients with uncomplicated falciparum malaria 50 mg AS as rectal suppository [0.86 - 2.55 mg/kg AS] | 90† | 0.58 | ||
[30] Navaratnam et al, 1998 | 12 healthy Malaysian adults 200 mg AS as rectal suppository | 448.5 | 1.43 | 0.95 | 796 |
Ref. | Subjects & Regimen | Cmax (ng/mL) | Tmax (hours) | Clearance (L/kg/hr) | Volume (L/kg) | Half-life (hours) | AUC (ng*hr/mL) |
---|---|---|---|---|---|---|---|
[49] Sirivichay et al, 2007 | 16 paediatric patients with uncomplicated falciparum malaria 10 mg/kg (n = 7) or 20 mg/kg (n = 9) AS as rectal suppositories | 898; 1535†a | 1.5; 2.0a | 1.3; 1.8a | 2403; 5633†a | ||
[50] Halpaap et al, 1998 | 12 paediatric patients with uncomplicated falciparum malaria 50 mg AS as rectal suppository [0.86 - 2.55 mg/kg AS] | 180† | 1.13 | ||||
[42] Awad et al, 2004 | 12 healthy Sudanese adults 200 mg AS as rectal suppository | 219.1† | 1.95 | 1.21 | 1185.17 | ||
[30] Navaratnam et al, 1998 | 12 healthy Malaysian adults 200 mg AS as rectal suppository | 385.6† | 1.80 | AUC0-t 965 | |||
Krishna et al, 2001 [15] | 34 Ghanaian children (8 months - 7 years) with moderate falciparum malaria Group 1: AS 10 mg/kg as rectal suppository, IV AS 2.4 mg/kg 12 hr later Group 2: AS 20 mg/kg AS as rectal suppository, IV AS 2.4 mg/kg 12 hr later Group 3: 2.4 mg/kg IV AS, 20 mg/kg AS as rectal suppository 12 hr later | Group 1: 682†a Group 2 & 3: 881†a | Group 1: 1.7a Tlag: 0.63a Group 2 & 3: 1.8a Tlag: 0.37a | Group 1: 2.6 Group 2 & 3: 3.9 | Group 1: 4.4a Group 2 & 3: 5.9a | Group 1: 0.79a Group 2 & 3: 0.85a | Group 1: 2787 †a Group 2 & 3: 3753†a |