Quercetin PK parameter estimates after first dose and at 4 months after multiple doses of quercetin in 8 pediatric patients receiving powder form. (A) Quercetin PK profiles show wide interindividual variability in absorption. (B) Quercetin PK parameter estimates. No significant differences were observed in Cmax, Tmax, and t½ between day 1 levels after a single dose of quercetin and at 4 months after multiple doses. Quercetin accumulation was not observed after 4 months of administration. Significantly higher clearance (CL/F; P < .01) and Vd/F (P < .01) were observed at 4 months after quercetin compared with the initial dose. (C) Quercetin dose escalation based on PKs and identification of the recommended dose. The first 3 patients underwent intrapatient dose escalation to a maximum of 1500 mg/d. Subsequent cohorts (3 patients each) were treated with escalating doses based on tolerability, safety, and quercetin exposure in the previous cohort. A weight-adjusted daily maximum dose of 4000 mg/d was considered the recommended dose and was selected for treatment of patients in the expansion cohort. Our PK model predicted no further increase in quercetin exposure beyond what is achieved by the currently recommended dose, likely because of enterohepatic circulation and first-pass metabolism.