Table 2

Parameter estimates of the final model describing piperaquine population pharmacokinetics in pregnant and nonpregnant women with uncomplicated malariaa

ParameterbCL/F (liters/h)VC/F (liters)Q1/F (liters/h)VP1/F (liters)Q2/F (liters/h)VP2/F (liters)MTT (h)No. of transit comp.F (%)σPregnancy covariate effect (%) on:
Population estimate (% RSE)60.2 (10.5)3,070 (12.5)427 (14.9)4,440 (17.8)160 (10.7)31,400 (9.55)2.04 (4.97)5 (fixed)100 (fixed)0.285 (5.47)45.0 (24.5)46.8 (35.6)
95% CI for population estimate49.6–74.22,400–3,930324–5753,210–6,300131–19626,500–38,3001.85–2.250.255–0.31425.1–69.118.2–86.0
% CV for IIV/BOV (% RSE)21.5 (27.0)39.5 (35.7)33.8 (28.8)45.8 (22.1)c56.3 (25.6)c
95% CI for IIV/BOV14.5–26.221.7–50.721.8–42.935.4–56.141.8–72.2
  • a Data are for 24 pregnant and 24 nonpregnant women. CL, elimination clearance; VC, central volume of distribution; Q, intercompartment clearance; VP, peripheral volume of distribution; MTT, mean absorption transit time; no. of transit comp., number of transit compartments; F, oral bioavailability; σ, additive residual error; IIV, interindividual variability; BOV, between-occasion variability.

  • b Population estimates are computed population mean values from NONMEM Relative standard error (RSE) was assessed by the nonparametric bootstrap method (n = 1,000 iterations, of which 848 minimized successfully) of the final pharmacokinetic model. RSE is calculated as 100 × (standard deviation/mean value). The 95% confidence interval (CI) is displayed as the 2.5 to 97.5 percentile of bootstrap estimates. Coefficient of variation (% CV) for interindividual variability and between-occasion variability were calculated as SQRT of [exp(estimated variance) − 1], where SQRT is the square root.

  • c Between-occasion variability.