NDLI: Population-pharmacokinetic/pharmacodynamic model of atractylodes lancea (Thunb.) DC. administration in patients with advanced-stage intrahepatic cholangiocarcinoma: a dosage prediction

Content Provider	Springer Nature : BioMed Central
Author	Saeheng, Teerachat Karbwang, Juntra Na-Bangchang, Kesara
Abstract	Background A recent phase 2A clinical study of Atractylodes lancea (Thunb.) DC. (AL) in patients with advanced-stage intrahepatic cholangiocarcinoma (iCCA) demonstrated significant reduction of the risk of tumor progression and mortality with a dose ranging from 1,000 to 2,000 mg. The present study aimed to determine the potential dosage regimen of AL for further phase 2B clinical study. Methods Plasma-concentration time profiles of total AL bioactivity and clinical efficacy in patients with advanced-stage iCCA were obtained from Phase 2 A study. The population pharmacokinetic (pop-PK) model was developed. The pop-PK model and Monte-Carlo (MC) simulation, in conjunction with maximum concentration of AL (Cmax) as a cut-off criterion, was performed and validated with clinical data. The optimal model was used to simulate further dosage regimens and clinical efficacy of AL. Results The pop-PK properties of total AL bioactivity were best described by a compartmental model with zero-order absorption (without delay) and linear clearance. None of the investigated covariates improved model accuracy.The developed pop-PK with MC simulations following once-daily dosing of 1,000 mg and 2,000 mg adequately predicted the clinical efficacy (tumor progression and mortality). The once-daily dose of 2,500 mg is recommended for further phase 2B clinical study due to its relatively high efficacy on tumor progression inhibition (73%) and mortality rate reduction (71%) without excessive number of the administered capsules (23 capsules) and low risk of toxicities (<5%). Conclusions The applied pop-PK model with MC simulation, along with the appropriate cut-off pharmacokinetic parameters, can be used as a potential tool for supporting dosage prediction and selection for clinical studies, and thus reducing the rate of drug development failures. Trial registration www.thaiclinicaltrials.org , WHO ICTRP search, TCTR20210129007 , Registed 29 January 2021.
Related Links	https://bmccomplementmedtherapies.biomedcentral.com/counter/pdf/10.1186/s12906-024-04618-8.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	26627671
DOI	10.1186/s12906-024-04618-8
Journal	BMC Complementary Medicine and Therapies
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2024-11-06
Access Restriction	Open
Subject Keyword	Complementary & Alternative Medicine Internal Medicine Chiropractic Medicine Atractylodes Lancea Population-pharmacokinetic model Intrahepatic cholangiocarcinoma Biliary tract cancer Dose prediction Clinical study
Content Type	Text
Resource Type	Article
Subject	Complementary and Alternative Medicine
Journal Impact Factor	3.3/2023
5-Year Journal Impact Factor	3.6/2023

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