Background and objectives: Baicalein, a flavonoid isolated from the root of Scutellaria baicalensis Georgi, is a neuroprotective agent under development to treat Parkinson's disease. This study investigated the pharmacokinetics, safety and tolerability of baicalein after a multiple-ascending-dose protocol in healthy Chinese volunteers.
Methods: In this single-center, double-blind, placebo-controlled, parallel-group study, participants were randomized to receive baicalein (n = 8 per dose regimen) or placebo (n = 2 per dose regimen). Dosing regimens were 200, 400, and 800 mg once daily on days 1 and 10, twice daily on days 3-9. Plasma, urine, and feces samples were assayed for baicalein and its predominant metabolite baicalin using validated HPLC-MS/MS methods. Pharmacokinetic parameters were computed using standard non-compartmental analysis. Dose proportionality was assessed with a method combining equivalence criterion and power model. Drug safety and tolerability were assessed by monitoring adverse events and laboratory parameters.
Results: Thirty-three of 36 enrolled participants completed the study. A total of 44 adverse events occurred in 23 participants. A steady-state concentration of analytes in plasma was achieved on day 8 after repeated dosing. Analytes concentrations and exposure increased with increasing dose. The dose proportionality constant (β) for AUCss of baicalein and baicalin was 0.922 (90 % confidence interval, 0.650-1.195) and 0.942 (90 % confidence interval, 0.539-1.345), respectively. The accumulation index varied from 1.66 to 2.07 for baicalein and from 1.68 to 2.45 for baicalin.
Conclusion: In dose range of 200-800 mg, multiple-dose oral baicalein administration was safe and well tolerated, dose proportionality was inconclusive, and no serious accumulation of baicalein was observed.