Phase I clinical trial to evaluate the safety and pharmacokinetics of capsule formulation of the standardized extract of Atractylodes lancea

Abstract

Background and aim Atractylodes lancea (AL) has been demonstrated in a series of studies to be a potential candidate for the treatment of cholangiocarcinoma. The aim of the current study was to evaluate the safety and pharmacokinetics of the capsule formulation of the standardized AL extract in healthy Thai participants. Experimental procedure Forty-eight healthy Thai participants who fulfilled the inclusion and had none of the exclusion criteria were allocated to two study groups. The group 1 participants were randomized to receive a single oral dose of 1,000 mg of AL or placebo (20:4 participants). The group 2 participants were randomized to receive daily oral doses of 1,000 mg AL or placebo daily for 21 days (20:4 participants). Safety and tolerability of the two AL regimens were monitored. Blood samples were collected for measurement of atractylodin concentrations by HPLC and pharmacokinetic analysis was performed using model-dependent and model-independent analysis. Results and conclusion The AL extract was well tolerated in both groups. Atractylodin was rapidly absorbed but with low systemic exposure and residence time. There was no difference in the pharmacokinetic parameters of atractylodin following a single or multiple dosing, suggesting the absence of accumulation and dose-dependency in human plasma after continuous dosing for 21 days. The information on human pharmacokinetics of AL, when given as capsule formulation of the standardized extract, would assist in further dose optimization in cholangiocarcinoma patients with the defined pharmacokinetic-pharmacodynamic relationship.

Clinical safety and pharmacokinetic evaluation of aqueous extract of Cocculus hirsutus, an anti-viral phytopharmacetical drug as a potential for the treatment of dengue and COVID-19

“…In recent years, many pharmacokinetic studies of herbal medicines have been conducted. However, unlike allopathic medicines, the pharmacological actions of herbal medicine are thought to be due to the synergistic effects of multiple components, and multi-targets/multipathways [21]. Therefore, the pharmacokinetics of herbal medicine is relatively more complex than synthetic drugs.…”

LIPOPHILICITY, AQUEOUS SOLUBILITY, AND DEGREE OF IONIZATION OF ATRACTYLODIN AND Β-Eudesmol, THE BIOACTIVE COMPOUNDS ISOLATED FROM ATRACTYLODES LANCEA

“…Oral absorption of actractylodin and βeudesmol are expected to be relatively poor and erratic and are influenced by drug pharmaceutical formulations as well as in vivo factors [54]. The in vitro-in vivo relationship is predictable, which is supported by the results of phase I pharmacokinetic study of atractylodin by compartmental analysis (1-compartment) [10]. The absorption rate constant (Ka) was approximately 0.8 l/h, and the membrane permeability obtained from back-calculation of the Ka CONCLUSION suggested compounds to be moderately permeable.…”

“…The CMC (Chemistry, Manufacturing, and Control) capsule formulation of the standardized extract of A. lancea has been developed for the clinical development phase. Recently, a phase I clinical trial to evaluate the safety, pharmacokinetics and immunomodulatory activity of the CMC capsule formulation of the standardized extract of A. lancea has been conducted in 48 healthy Thai subjects following 1,000 mg/kg body weight given as a single oral dose or as daily doses for 14 d [10]. This starting dose in human (1,000 mg/kg body weight) is about 50% of the maximum recommended starting dose (MRSD) [11] initially estimated from animal toxicology data [6,7].…”

Atractylodes lancea for cholangiocarcinoma: Modulatory effects on CYP1A2 and CYP3A1 and pharmacokinetics in rats and biodistribution in mice

“…Phase I clinical trial to evaluate the safety and pharmacokinetics of the formulated AL has been completed [ 15 ]. Results suggest a satisfactory safety profile when given orally at a single or daily dose of 1,000 mg [ 15 ]. Atractylodin (ATD: active compound) was well absorbed, reaching maximum concentration (t max ) within 1 hour.…”

“…Atractylodin (ATD: active compound) was well absorbed, reaching maximum concentration (t max ) within 1 hour. The elimination half-life (t 1/2 ) was short (1.23 hours) [ 15 ]. Phase II clinical trial in patients with advanced stage cholangiocarcinoma is underway.…”