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Table 1 Identification of resistance/reduced sensitivity of P. falciparum isolates to artesunate (AS)-mefloquine (MQ) combination therapy was analysed based on clinico-parasitological response, and in vitro sensitivity and systemic drug exposure during the acute phase of infection and relationship with pfmdr1 copy number in 17 cases with treatment failure following a three-day combination regimen

From: Identification of resistance of Plasmodium falciparum to artesunate-mefloquine combination in an area along the Thai-Myanmar border: integration of clinico-parasitological response, systemic drug exposure, and in vitro parasite sensitivity

Systemic drug exposure Case No. Parasite slope half-life (h)a In vitro sensitivity (IC50: nM)b Pfmdr1 copy number MQ/DHA Systemic exposure Conclusion on cause(s) of treatment failure
    AS MQ   AUC0-7d/ AUC0-24h/ Day Re  
Adequate DHA exposure alone (n=5) 1 3.12 Reduced (3.5±0.42) Resistant (58.8±5.1) >1 7.55c 610 (day 21) -Possible AS resistant
-MQ resistant + Inadequate MQ exposure
-Predicted by increased in pfmdr1 copy number
2 3.56 Reduced (4.8±1.07) Resistant (69.5±4.7) >1 8.02c 100 (day 28) -Possible AS resistant
-MQ resistant + Inadequate MQ exposure
-Predicted by increased in pfmdr1 copy number
3 4.23 Sensitive (1.2±0.27) Sensitive (10.6±1.9) 1 6.98c 300 (day 28) -Inadequate MQ exposure
4 3.88 Sensitive (0.7±0.13) Sensitive (6.6±0.4) 1 7.99c 600 (day 33) -Inadequate MQ exposure
5 3.42 Sensitive (0.9±0.10) Sensitive (19.4±0.7) >1 8.07c 720 (day 14) -Inadequate MQ exposure
-Predicted by increased in pfmdr1 copy number
Adequate MQ exposure alone (n=5) 6 3.55 Reduced (3.0±0.06) Resistant (45.3±3.1) >1 320d 324 (day 27) -Possible AS resistant + Inadequate DHA exposure
-MQ resistant
-Predicted by increased in pfmdr1 copy number
7 3.39 Reduced (3.1±0.05) Resistant (70.3±6.3) >1 208d 212 (day 28) -Possible AS resistant + Inadequate DHA exposure
-MQ resistant
-Predicted by increased in pfmdr1 copy number
8 3.56 Reduced (4.2±0.07) Resistant (50.0±4.2) >1 309d 489 (day 21) -Possible AS resistant + Inadequate DHA exposure
-Mefloquine resistant
-Predicted by increased in pfmdr1 copy number
  9 3.64 Sensitive (1.8±0.30) Resistant (55.3±4.4) >1 378d 510 (day 28) - Inadequate DHA concentration
-MQ resistant
-Predicted by pfmdr1 copy number
10 3.22 Sensitive (1.4) Resistant (35.0±2.9) >1 489d 402 (day 21) - Inadequate DHA exposure
-MQ resistant
-Predicted by pfmdr1 copy number
Adequate DHA and MQ exposure (n=7) 11 3.97 Reduced (2.9±0.01) Resistant (118.4±6.1) >1 - 1,250 (day 17) -Possible AS resistant
-MQ resistant,
-Predicted by increased in Pfmdr1 copy number
12 3.45 Reduced (3.7±0.32) Resistant (95.8±5.4) >1 - 578 (day 14) -Possible AS resistant
-MQ resistant
-Predicted by increased in Pfmdr1 copy number
13 3.33 Sensitive (1.7±0.16) Resistant (28.8±5.5) >1 - 102 (day 35) -MQ resistant
-Predicted by pfmdr1 copy number
14 3.56 Sensitive (1.9±0.10) Resistant (60.8±7.1) >1 - 620 (day 14) -MQ resistant
-Predicted by pfmdr1 copy number
15 3.65 Reduced (3.7±0.21) Resistant (25.5±0.2) 1 - 610 (day 24) -Possible AS resistant
-MQ resistant
16 3.56 Reduced (5.2±0.85) Sensitive (16.6±0.8 1 - 107 (day 35) -Possible AS resistant
  17 3.44 Sensitive (0.9±0.08) Sensitive (16.5±2.4) 1 - 67 (day 42) -Other host-related factors
  1. a Delayed parasite slope half-life if >2.99 h.
  2. b Mean + SD of three experiments, triplicate each.
  3. c MQ AUC 0-7d which was lower than the lower limit of 95% CI (8.48 mg.day/ml).
  4. d DHA AUC 0-24h which was lower than the lower limit of 95% CI (8.48 ng.h/ml).
  5. e Day of recrudescence.