Table 4

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

ParameterbCL/F (liters/h)V/F (liters)MTT (h)No. of transit comp.F (%)σCovariate effect on F (%)
PregnancyParasitemia
Population estimate (% RSE)78.0 (7.00)129 (7.30)0.982 (5.30)7 (fixed)100 (fixed)0.580 (5.11)−37.5 (17.2)27.8 (12.7)
95% CI for population estimate67.4–88.6111–1490.890–1.090.523–0.63424.0–49.021.3–37.3
% CV for IIV/BOV (% RSE)12.8 (27.7)50.9 (15.7)c30.3 (24.8)
95% CI for IIV/BOV8.70–16.041.8–59.620.9–35.7
  • a Data are for 24 pregnant and 24 nonpregnant women. CL, elimination clearance; V, 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 Computed population mean values from NONMEM are calculated for a typical patient with a body weight of 48.5 kg and an initial logarithmic parasitemia of 3.98. Relative standard error (RSE) was assessed by the nonparametric bootstrap method (n = 1,000 iterations, of which 919 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 are calculated as SQRT of [exp(estimated variance) − 1], where SQRT is the square root.

  • c Between-occasion variability.