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Table 2 Analysis of contribution of in vitro parasite sensitivity and systemic drug exposure during acute phase of infection and relationship with pfmdr1 copy number in patients with sensitive response following treatment with a three-day artesunate (AS)-mefloquine (MQ) 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

Drug concentrations Case No. Parasite slope half-life (h)a In vitro sensitivity (IC50, nM)b Pfmdr1 copy number MQ AUC0-7d/ DHA AUC0-24h/ Conclusion on parasite sensitivity and adequacy of systemic drung exposure
    AS MQ    
Adequate DHA exposure alone (n= 4) 18 2.90 Reduced (2.4±1.0) Resistant (34.5±3.2) >1 8.40c -Possible AS resistant
-MQ resistant + Inadequate MQ exposure
19 2.97 Sensitive (1.1±0.15) Sensitive (8.0±1.4) 1 6.78c -AS sensitive
-MQ sensitive + Inadequate MQ exposure
-Predicted by pfmdr1 copy number
20 3.01 Sensitive (2.0±0.25) Resistant (31.3±1.6) 1 7.77c - AS sensitive
- MQ resistant + Inadequate MQ exposure
-Predicted by pfmdr1 copy number
21 2.78 Sensitive (1.8±0.13) Sensitive (17.5±3.0) 1 7.09c -AS sensitive
- MQ sensitive + Inadequate MQ exposure
-Predicted by pfmdr1 copy number
Adequate MQ exposure alone (n=9) 22 3.11 Reduced (3.2±0.15) Resistant (90.0±16.5) 1 402d -Possible AS resistant + Inadequate DHA exposure
-MQ resistant
-Predicted by pfmdr1 copy number
23 3.23 Sensitive (0.4±0.04) Sensitive (14.6±2.2) 1 389d -AS sensitive + Inadequate DHA exposure
-MQ sensitive
-Predicted by pfmdr1 copy number
24 2.78 Sensitive (0.3±0.10) Sensitive (13.7±2.4) 1 390d -AS sensitive+ Inadequate DHA exposure
-MQ sensitive
-Predicted by pfmdr1 copy number
25 3.01 Sensitive (1.8±0.31) Resistant (47.5±1.7) >1 391d -AS sensitive + Inadequate DHA exposure
-MQ resistant
26 2.89 Sensitive (1.6±0.30) Sensitive (20.9±0.5) 1 398d -AS sensitive+ Inadequate DHA exposure
-MQ sensitive
-Predicted by pfmdr1 copy number entration
27 2.77 Sensitive (1.6±0.24) Resistant (27.1±1.0) 1 450d -Possible AS resistant + Inadequate DHA exposure
-MQ sensitive
-Predicted by pfmdr1 copy number
28 3.01 Sensitive (1.9±0.35) Sensitive (18.5±2.4) 1 409d -AS sensitive + Inadequate DHA exposure
-MQ sensitive
-Predicted by pfmdr1 copy number
29 2.89 Sensitive (1.0±0.03) Sensitive (8.1±0.1) 1 379d -AS sensitive + Inadequate DHA exposure
-MQ sensitive
-Predicted by pfmdr1 copy number
30 3.01 Sensitive (2.2±0.16) Sensitive (19.1±1.0) 1 423d -AS sensitive + Inadequate DHA exposure
-MQ sensitive
-Predicted by pfmdr1 copy number
Adequate DHA and MQ exposure (n=6) 31 2.67 Reduced (3.4±0.44) Resistant (100.7±16.8) >1 - -Possible AS resistant
-MQ resistant
32 2.89 Reduced (3.8±0.62) Resistant (62.2±4.6) >1 - -Possible AS resistant
-MQ resistant
33 3.00 Reduced (3.3±0.37) Resistant (60.0±4.2) >1 - -Possible AS resistant
-MQ resistant
34 3.00 Sensitive (1.4±0.31) Sensitive (6.8±0.5) 1 - -AS sensitive
-MQ sensitive
-Predicted by pfmdr1 copy number
35 2.09 Sensitive (0.9±0.13) Resistant (25.1±0.2) 1 - -AS sensitive
-MQ resistant
-Predicted by pfmdr1 copy number
36 2.89 Sensitive (1.6±0.19) Sensitive (21.2±0.3) 1 - -AS sensitive
-MQ sensitive
-Predicted by pfmdr1 copy number
Inadequate DHA and MQ exposure (n=2) 37 2.90 Sensitive (1.5±0.23) Sensitive (14.3±2.7) >1 5.34c -AS sensitive
234d -MQ sensitive
38 3.01 Sensitive (1.9±0.28) Sensitive (22.1±0.4) 1 7.09c -AS sensitive
209d -MQ sensitive
        -Predicted by pfmdr1 copy number
  1. a Delayed parasite slope half-life if > 2.99 h.
  2. b Mean ± SD of 3 experiments, triplicate each.
  3. c MQ AUC 0-7d which was lower than the lower limit of 95% CI (8.48 μg.day/ml).
  4. d DHA AUC 0-24h which was lower than the lower limit of 95% CI (8.48 ng.h/ml).