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. 2021 Jan 6;20:18. doi: 10.1186/s12936-020-03553-6

Table 5.

Multivariate analysis of log-transformed Amodiaquine and Desethylamodiaquine pharmacokinetic parameters following artesunate-amodiaquine fixed-dose combination treatment of Ghanaian patients with uncomplicated P. falciparum malaria (geometric Mean Ratios (GMR) and 95% Confidence Intervals (CI))

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,