Parameter^{a} | Population estimate^{b} | 95% CI^{c} | % RSE^{d} |
---|---|---|---|

Primary | |||

Amodiaquine | |||

K (h_{a}^{−1}) | 0.515 | 0.439–0.587 | 6.93 |

Lag time (h) | 0.395 | 0.359–0.456 | 7.48 |

CL/F_{AQ} (liters/h) | 2,530 | 2,360–2,760 | 3.82 |

V_{C}/F_{AQ} (liters) | 4,850 | 3,750–5,810 | 10.2 |

Q_{1}/F_{AQ} (liters/h) | 2,750 | 2,450–3,090 | 5.53 |

V_{P}_{1}/F_{AQ} (liters) | 29,000 | 25,600–34,100 | 6.90 |

σ_{AQ} | 0.0479 | 0.0372–0.0671 | 6.92 |

Desethylamodiaquine | |||

CL/F_{DEAQ} (liters/h) | 34.3 | 31.4–37.7 | 4.43 |

V/_{C}F_{DEAQ} (liters) | 197 | 167–233 | 8.13 |

Q_{1}/F_{DEAQ} (liters/h) | 161 | 141–180 | 5.98 |

V_{P}_{1}/F_{DEAQ} (liters) | 2,670 | 2,370–2,960 | 5.41 |

Q_{2}/F_{DEAQ} (liters/h) | 26.0 | 22.9–29.4 | 5.88 |

V_{P}_{2}/F_{DEAQ} (liters) | 5,700 | 5,200–6,410 | 5.16 |

σ_{DEAQ} | 0.0416 | 0.0279–0.0548 | 8.57 |

Covariate effects | |||

Age effect on CL/F_{AQ} (% reduction per year) | 1.36 | 0.321–2.30 | 34.6 |

Pregnancy effect on Lag-time (% decrease) | 41.6 | 32.2–57.3 | 16.5 |

Interindividual variability (% CV) | |||

CL/F_{AQ} (liters/h) | 0.0455 (21.6) | 0.0250–0.700 | 23.3 |

V/_{C}F_{AQ} (liters) | 0.349 (64.6) | 0.198–0.523 | 22.4 |

Q_{1}/F_{AQ} (liters/h) | 0.0639 (25.7) | 0.0259–0.126 | 35.3 |

V_{P}_{1}/F_{AQ} (liters) | 0.0652 (26.0) | 0.0180–0.103 | 31.8 |

CL/F_{DEAQ} (liters/h) | 0.0535 (23.4) | 0.0301–0.0833 | 25.0 |

V/_{C}F_{DEAQ} (liters) | 0.210 (48.3) | 0.0000212–0.369 | 44.9 |

V_{P}_{2}/F_{DEAQ} (liters) | 0.0321 (18.1) | 0.00000534–0.134 | 67.3 |

Lag time (h) | 0.325 (62.0) | 0.141–0.474 | 27.4 |

Interoccasion variability (% CV) | |||

F | 0.0575 (24.3) | 0.0435–0.0748 | 13.1 |

Pharmacodynamics | |||

BASE (infections per year) | 2.72 | 1.24–6.14 | 38.7 |

PC_{50 DEAQ} (ng/ml) | 7.08 | 2.13–22.1 | 68.7 |

Secondary [median (range)]^{e} | Total (n = 46) | Pregnant (n = 27) | Postpartum (n = 19) |

C_{max AQ} (ng/ml) | 30.2 (16.1–54.5) | 30.3 (17.9–54.5) | 29.4 (16.1–50.7) |

T_{max AQ} (h) | 1.69 (0.938–2.55) | 1.47 (0.938–2.54) | 1.78 (1.12–2.55) |

t_{1/2 AQ} (h) | 15.6 (11.1–27.1) | 18.4 (11.1–27.1) | 14.6 (11.4–22.8) |

AUC_{5 AQ} (h · ng/ml) | 586 (265–890) | 608 (350–890) | 558 (265–811) |

C_{max DEAQ} (ng/ml) | 350 (221–544) | 349 (221–478) | 362 (253–544) |

T_{max DEAQ} (h) | 2.97 (1.66–4.72) | 2.71 (1.66–4.72) | 3.12 (2.13–4.13) |

t_{1/2 DEAQ} (days) | 12.4 (8.63–23.3) | 12.3 (9.33–23.3) | 12.6 (8.46–15.8) |

AUC_{60 DEAQ} (h · μg/ml) | 36.8 (19.0–69.9) | 37.1 (19.0–69.9) | 36.6 (22.1–59.8) |

↵a AQ, amodiaquine; DEAQ, desethylamodiaquine;

*K*, absorption rate constant; Lag time, absorption lag time; CL/_{a}*F*, oral clearance;*V*/_{C}*F*, central volume of distribution;*Q*/*F*, intercompartmental clearance;*V*/_{P}*F*, peripheral volume of distribution;*F*, relative bioavailability; σ, residual error variance; BASE, baseline hazard; PC_{50 DEAQ}, 50% protective concentration;*C*_{max}, maximum concentration;*T*_{max}, time to maximum concentration;*t*_{1/2}, terminal elimination half-life; AUC, area under the concentration-time curve from time zero to_{x}*x*days.↵b Computed population mean parameter estimates from NONMEM are calculated for a typical patient with a body weight of 48 kg and age of 23 years. The coefficient of variation (% CV) for interindividual variability is calculated as [exp(estimate) − 1]

^{1/2}× 100.↵c Computed from the nonparametric bootstrap method of the final pharmacokinetic model (

*n*= 1,000) and pharmacodynamic model (*n*= 500).d Calculated as 100 × (standard deviation/mean value).

↵e Secondary-parameter estimates are calculated from the Bayesian post hoc estimates.