Table 5.
GMR | 95% CI | p-value | GMR | 95% CI | p-value | |
---|---|---|---|---|---|---|
Area under the Curve (AUC0-∞) | Amodiaquine (n = 196) | Desethylamodiaquine (n = 210) | ||||
Age category: < 1 versus ≥ 5 years | 5.42 | 1.20 to 24.57 | 0.029 | 1.12 | 0.38 to 3.29 | 0.84 |
Age category: 1–4 versus ≥ 5 years | 1.85 | 0.60 to 5.71 | 0.28 | 0.81 | 0.36 to 1.79 | 0.60 |
Baseline Fever (Temperature: ≥ 37.5 °C) | 1.44 | 1.01 to 2.04 | 0.045 | 1.13 | 0.87 to 1.47 | 0.37 |
Underweight-for-age: WAZ < − 2.0 vs WAZ ≥ − 2.0 | 0.82 | 0.45 to 1.48 | 0.50 | 1.15 | 0.72 to 1.84 | 0.55 |
Underweight-for-age: NA vs WAZ ≥ − 2.0 | 0.82 | 0.26 to 2.57 | 0.74 | 0.68 | 0.31 to 1.53 | 0.35 |
Dose (mg/kg) | 1.04 | 1.01 to 1.06 | 0.001 | 1.02 | 1.00 to 1.04 | 0.041 |
Sex: Female (vs. male) | 0.74 | 0.54 to 1.01 | 0.058 | 0.87 | 0.68 to 1.12 | 0.28 |
Parasite density < 100,000 (vs ≥ 100,000/ µL) | 0.91 | 0.58 to 1.42 | 0.67 | 1.13 | 0.81 to 1.58 | 0.46 |
Anaemia: Hb < 8.0 g/dL | 1.44 | 0.87 to 2.36 | 0.15 | 1.20 | 0.81 to 1.78 | 0.35 |
Site: Navrongo (vs Kintampo) | 0.16 | 0.09 to 0.27 | < 0.001 | 1.12 | 0.73 to 1.71 | 0.61 |
Prior AQ use: Day 0 DEAQ > 20 ng/mL | 1.23 | 0.93 to 1.63 | 0.14 |
Maximum concentration (Cmax) | Amodiaquine (n = 217) | Desethylamodiaquine (n = 211) | ||||
---|---|---|---|---|---|---|
Age category: < 1 versus ≥ 5 years | 2.69 | 0.83 to 8.73 | 0.099 | 0.73 | 0.26 to 2.00 | 0.54 |
Age category: 1–4 versus ≥ 5 years | 2.30 | 0.93 to 5.65 | 0.071 | 0.86 | 0.40 to 1.85 | 0.69 |
Baseline Fever (Temperature: ≥ 37.5 °C) | 1.57 | 1.18 to 2.09 | 0.002 | 1.17 | 0.91 to 1.51 | 0.22 |
Underweight-for-age: WAZ < -2.0 vs WAZ ≥ − 2.0 | 0.63 | 0.38 to 1.05 | 0.075 | 1.08 | 0.69 to 1.70 | 0.72 |
Underweight-for-age: NA vs WAZ ≥ − 2.0 | 0.95 | 0.38 to 2.36 | 0.90 | 0.69 | 0.32 to 1.51 | 0.36 |
Dose (mg/kg) | 1.03 | 1.01 to 1.05 | 0.001 | 1.01 | 1.00 to 1.03 | 0.14 |
Sex: Female (vs. male) | 0.80 | 0.62 to 1.05 | 0.105 | 0.85 | 0.67 to 1.07 | 0.17 |
Parasite density < 100,000 (vs ≥ 100,000/µL) | 0.77 | 0.53 to 1.13 | 0.18 | 1.09 | 0.79 to 1.50 | 0.62 |
Anaemia: Hb < 8.0 g/dL | 1.72 | 1.12 to 2.64 | 0.013 | 1.23 | 0.85 to 1.79 | 0.27 |
Site: Navrongo (vs Kintampo) | 0.18 | 0.12 to 0.28 | < 0.001 | 1.36 | 0.90 to 2.05 | 0.14 |
Prior AQ use: Day 0 DEAQ > 20 ng/mL | 1.18 | 0.90 to 1.54 | 0.23 |
Apparent Clearance (Cl/f) | Amodiaquine (n = 196) | Desethylamodiaquine (n = 210) | ||||
---|---|---|---|---|---|---|
Age category: < 1 versus ≥ 5 years | 0.20 | 0.04 to 0.89 | 0.035 | 0.95 | 0.32 to 2.81 | 0.92 |
Age category: 1–4 versus ≥ 5 years | 0.55 | 0.18 to 1.71 | 0.30 | 1.27 | 0.57 to 2.84 | 0.56 |
Baseline Fever (Temperature: ≥ 37.5 °C) | 0.69 | 0.49 to 0.99 | 0.042 | 0.88 | 0.67 to 1.15 | 0.34 |
Underweight-for-age: WAZ < -2.0 vs WAZ ≥ − 2.0 | 1.23 | 0.67 to 2.23 | 0.50 | 0.87 | 0.54 to 1.39 | 0.56 |
Underweight-for-age: NA vs WAZ ≥ − 2.0 | 1.22 | 0.39 to 3.84 | 0.73 | 1.47 | 0.65 to 3.33 | 0.35 |
Dose (mg/kg) | 1.00 | 0.98 to 1.02 | 0.79 | 1.01 | 1.00 to 1.03 | 0.093 |
Sex: Female (vs. male) | 1.34 | 0.98 to 1.85 | 0.070 | 1.13 | 0.88 to 1.45 | 0.34 |
Parasite density < 100,000 (vs ≥ 100,000/µL) | 1.10 | 0.7 to 1.71 | 0.69 | 0.88 | 0.63 to 1.24 | 0.46 |
Anaemia: Hb < 8.0 g/dL | 0.70 | 0.42 to 1.16 | 0.16 | 0.83 | 0.56 to 1.24 | 0.37 |
Site: Navrongo (vs Kintampo) | 6.82 | 4.00 to 11.63 | < 0.001 | 0.97 | 0.63 to 1.50 | 0.91 |
Prior AQ use: Day 0 DEAQ > 20 ng/mL | 0.81 | 0.61 to 1.07 | 0.13 |
Apparent Volume of distribution (Vd/f) | Amodiaquine (n = 152) | Desethylamodiaquine (n = 209) | ||||
---|---|---|---|---|---|---|
Age category: < 1 versus ≥ 5 years | 0.62 | 0.07 to 5.39 | 0.66 | 0.74 | 0.19 to 2.82 | 0.65 |
Age category: 1–4 versus ≥ 5 years | 0.67 | 0.11 to 4.21 | 0.67 | 0.84 | 0.32 to 2.19 | 0.72 |
Baseline Fever (Temperature: ≥ 37.5 °C) | 0.67 | 0.42 to 1.09 | 0.10 | 0.71 | 0.50 to 1.00 | 0.050 |
Underweight-for-age: WAZ < − 2.0 vs WAZ ≥ − 2.0 | 1.44 | 0.7 to 2.99 | 0.32 | 0.91 | 0.50 to 1.65 | 0.76 |
Underweight-for-age: NA vs WAZ ≥ − 2.0 | 1.16 | 0.18 to 7.26 | 0.88 | 0.95 | 0.36 to 2.51 | 0.91 |
Dose (mg/kg) | 1.01 | 0.98 to 1.04 | 0.42 | 1.02 | 1.00 to 1.05 | 0.044 |
Sex: Female (vs. male) | 0.93 | 0.61 to 1.42 | 0.74 | 1.23 | 0.90 to 1.7 | 0.20 |
Parasite density < 100,000 (vs ≥ 100,000/µL) | 0.78 | 0.43 to 1.4 | 0.41 | 1.19 | 0.76 to 1.85 | 0.45 |
Anaemia: Hb < 8.0 g/dL | 0.54 | 0.28 to 1.05 | 0.070 | 0.75 | 0.45 to 1.25 | 0.27 |
Site: Navrongo (vs Kintampo) | 4.30 | 2.20 to 8.39 | < 0.001 | 0.76 | 0.44 to 1.31 | 0.32 |
Prior AQ use: Day 0 DEAQ > 20 ng/mL | 0.86 | 0.59 to 1.24 | 0.41 |
Elimination half-life (t½) | Amodiaquine (n = 152) | Desethylamodiaquine (n = 208) | ||||
---|---|---|---|---|---|---|
Age category: < 1 versus ≥ 5 years | 1.82 | 0.59 to 5.6 | 0.29 | 1.05 | 0.49 to 2.21 | 0.91 |
Age category: 1–4 versus ≥ 5 years | 1.78 | 0.75 to 4.18 | 0.19 | 0.90 | 0.52 to 1.53 | 0.69 |
Baseline Fever (Temperature: ≥ 37.5 °C) | 0.95 | 0.72 to 1.24 | 0.70 | 0.85 | 0.70 to 1.03 | 0.103 |
Underweight-for-age: WAZ < − 2.0 vs WAZ ≥ − 2.0 | 0.98 | 0.65 to 1.48 | 0.92 | 0.95 | 0.68 to 1.32 | 0.74 |
Underweight-for-age: NA vs WAZ ≥ − 2.0 | 1.39 | 0.59 to 3.29 | 0.45 | 0.84 | 0.49 to 1.45 | 0.52 |
Dose (mg/kg) | 1.01 | 0.99 to 1.02 | 0.54 | 1.01 | 1.00 to 1.02 | 0.18 |
Sex: Female (vs. male) | 0.74 | 0.58 to 0.94 | 0.013 | 1.08 | 0.90 to 1.29 | 0.41 |
Parasite density < 100,000 (vs ≥ 100,000/µL) | 0.84 | 0.61 to 1.17 | 0.31 | 1.41 | 1.09 to 1.81 | 0.008 |
Anaemia: Hb < 8.0 g/dL | 0.94 | 0.64 to 1.36 | 0.73 | 0.91 | 0.69 to 1.21 | 0.52 |
Site: Navrongo (vs Kintampo) | 0.85 | 0.58 to 1.24 | 0.39 | 0.86 | 0.63 to 1.16 | 0.31 |
Prior AQ use: Day 0 DEAQ > 20 ng/mL | 1.08 | 0.88 to 1.32 | 0.48 |
WAZ Weight for Age z-score, NA Not applicable (WAZ score only calculated for children ≤ 5 years), AQ amodiaquine, DEAQ desethylamodiaquine,