Population Pharmacokinetics of Phosphocreatine and Its Metabolite Creatine in Children With Myocarditis

Figures

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  FIGURE 1. The concentration-time plots of PCr and Cr. The black lines are the mean concentration-time curves and circles are the observations.

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  FIGURE 2. The proposed pharmacokinetic structural model of PCr and Cr in pediatric patients. Equations (8)–(11) were used to describe this model. Dose, dosage in the PCr central compartment (the zero-order administration rate A0); CLPCr, clearance of the PCr central compartment; QPCr, intercompartmental clearance between the PCr central and peripheral compartments; VcPCr, distribution volume of the PCr central compartment; VpPCr, distribution volume of the PCr peripheral compartment; CLCr, clearance of the Cr central compartment; QCr, intercompartmental clearance between the Cr central and peripheral compartments; VcCr, distribution volume of the Cr central compartment; VpCr, distribution volume of the Cr peripheral compartment; baseCr, the endogenous Cr concentration before drug administration. Fm is the fraction of PCr metabolized to Cr. A1 and A2 are the PCr amount in the central and peripheral compartments, respectively; A3 and A4 are the Cr amount in the central and peripheral compartments, respectively.

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  FIGURE 3. The goodness-of-fit plots for the final pharmacokinetic model. (A) Conditional weighted residuals (CWRES) vs. time, the blue solid line is the linear regression trend line; (B) CWRES vs. population predictions, the blue solid line is the linear regression trend line; (C) observations vs. population predictions, the black solid line means the line of unity y = x; and (D) observations against individual predictions, the black solid line is the line of unity y = x.

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  FIGURE 4. Visual predictive check (VPC) from the final population pharmacokinetic model ((A) PCr concentration; (B) Cr concentration). The blue circles are the actual original observations. The red solid line is the observed 50th percentile and the red dashed lines mean the 5th and 95th percentiles of observations. The black solid line means predicted 50th percentile and the black dashed lines represent the 5th and 95th percentiles from the simulated observations (shadow means 95% confidence band).

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  FIGURE 5. The simulation curves from the final population pharmacokinetic model. Black solid line was the 50th percentile of simulated concentrations. Red line was the reference line.