TABLE 4.

Parameter estimates from the final pharmacokinetic-pharmacodynamic model for the piperaquine effect on absolute QTc_SSB interval^a

Parameter	Population estimateb (% RSE)c	95% CIc	IIV %CV (% RSE)c	95% CIc
QTcBaseline (ms)	421 (0.15)	420–423	17.0d (3.12)	16.0–18.0
Emax (ms)	35 (11.0)	29.0–44.2	49.1e (13.0)	34.1–62.4
EC50 (ng/ml)	209 (16.7)	155–296	119.3e (9.28)	88.7–152
γ	1.69 (11.6)	1.36–2.17
Effect of age on EC50 (%)	4.10 (19.5)	2.68–5.88
σ (ms)	11.6 (5.74)	10.5–13.2

^aAbbreviations: QTc_Baseline, baseline value of the QTc_SSB interval at enrollment; E_max, maximum QTc_SSB interval associated with drug effect; EC₅₀, piperaquine concentration needed to achieve 50% of the maximum drug effect; γ, shape function of the E_max model; σ, additive residual error (variance) of QTc_SSB interval measurements; IIV, interindividual variability.

^bComputed population mean parameter estimates from NONMEM.

^cBased on nonparametric bootstrap diagnostics (n = 1,000). Parameter precision is presented as relative standard deviation (%RSE), calculated as $100\times \frac{\text{standard deviation}}{\text{mean value}}$.

^dAdditive interindividual variability, presented as absolute variability on an arithmetic scale.

^eExponential interindividual variability, presented as the coefficient of variation (%CV), calculated as $100\times \sqrt{\text{exp}\left(\text{estimate}\right)-1}$.