case_images: PMC6929516_01
case_images: Measurements of eculizumab (ECZ) concentrations and pharmacokinetic (PK) estimation performed at Cincinnati Children's Hospital Medical Center. (A) Black circles show ECZ concentrations observed in this patient at 2 years old, receiving 300 mg doses of eculizumab, as indicated by arrows. The solid line represents the individual PK curve estimated with the Bayesian estimation method using MW-Pharm3.82 and five well-captured observations. The dashed line represents the population mean PK curve based on a body weight of 14 kg. As prior PK information in Bayesian estimation, we used reported PK parameters (clearance: 14.6 mL/h per 70 kg; volume of distribution: 6.16 L per 70 kg) for patients with aHUS (U.S. Food and Drug Administration approval document) and inter-individual variability. This patient's clearance estimate allometrically adjusted by body weight was 8.7 mL/h per 70 kg, which was lower than the population mean. Estimated volume of distribution (4.9 L per 70 kg) was comparable to the reported population value. (B) This patient's eculizumab PK after 300 mg repeated dosing with 2-, 3-, and 4- week interval regimens were simulated using individual PK parameter estimates obtained in (A), shown as black and red solid lines at 2 years of age (14.0 kg) and 4 years of age (17.5 kg), respectively. Population mean PK profiles at 2 years of age are also displayed in dashed lines to compare.
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case_images: PMC6929516_01_fped-07-00519-g0001.jpg
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case_images: As a result, this patient's estimated PK profile was demonstrated (Figure 1A). PK simulations for this patient at 2 years of age showed that trough concentrations at 2- or 3-week dosing intervals were higher than the target concentrations (>=100 mug/mL) (Figure 1B). Reanalysis of PK suggested that the ECZ trough level at the 3-week interval was still >100 mug/mL (Figure 1B, red lines).