Challenges and Solutions of Pharmacokinetics for Efficacy and Safety of Traditional Chinese Medicine

et al. 2018

Pharmaceutics

Stauntonia hexaphylla leaf extract (YRA-1909), which is widely used for the antirheumatic properties, has been under phase 2 clinical trials in patients with rheumatoid arthritis since April 2017. Liquid chromatography-tandem mass spectrometric method while using liquid–liquid extraction with ethyl acetate was validated for the simultaneous determination of the major active components of YRA-1909, including chlorogenic acid (CGA), neochlorogenic acid (NCGA), cryptochlorogenic acid (CCGA), and their metabolites (i.e., caffeic acid (CA), caffeic acid 3-O-glucuronide (CA-3-G), caffeic acid 4-O-glucuronide (CA-4-G), and ferulic acid (FA)) in rat plasma and applied to a pharmacokinetic study of YRA-1909 in rats. Seven analytes were separated on Halo C18 while using gradient elution of formic acid and methanol, and then quantified in selected reaction monitoring mode whle using negative electrospray ionization. Following oral administration of YRA-1909 at doses of 25, 50, and 100 mg/kg to male Sprague-Dawley rats, CGA, NCGA, and CCGA were rapidly absorbed and metabolized to CA, CA-3-G, and CA-4-G. The area under the plasma concentration-time curve (AUClast) of CGA, NCGA, CCGA, and three metabolites linearly increased as the YRA-1909 dose increased. Other pharmacokinetic parameters were comparable among three doses studied. AUClast values for CA, CA-3-G, and CA-4-G exceeded those for CGA, NCGA, and CCGA.

Section: Introductionmentioning

confidence: 99%

Simultaneous Determination of Chlorogenic Acid Isomers and Metabolites in Rat Plasma Using LC-MS/MS and Its Application to A Pharmacokinetic Study Following Oral Administration of Stauntonia Hexaphylla Leaf Extract (YRA-1909) to Rats

Choi

et al. 2018

Pharmaceutics

Biomedical Chromatography

“…Traditional Chinese medicine is widely used in China owing to its high reputation for disease treatment and general health improvement (Li et al, ). However, the lack of scientific support for its efficacy makes it difficult for it to be understood and accepted by both health authorities and the public (Li, Qi, Liu, Zhou, & Wen, ).…”

Section: Discussionmentioning

confidence: 99%

A sensitive HPLC–MS/MS method for the simultaneous determination of anemoside B4, anemoside A3 and 23‐hydroxybetulinic acid: Application to the pharmacokinetics and liver distribution of Pulsatilla chinensis saponins

Xie

Lian

et al. 2017

Pulsatilla chinensis saponins, the major active components in the herb, have drawn great attention as potential hepatitis B virus infection and hepatoma treatments. Here, a sensitive and accurate HPLC-MS/MS method was established for simultaneous determination of three saponins - anemoside B4, anemoside A3 and 23-hydroxybetulinic acid - in rat plasma and liver, and fully validated. The method was successfully applied to a pharmacokinetics and liver distribution study of P. chinensis saponins. Consequently, 23-hydroxybetulinic acid, with an extremely low content in the P. chinensis saponins, exhibited the highest exposure in the liver and in sites before and after hepatic disposition, namely, in the portal vein plasma and systemic plasma, followed by anemoside B4, which showed the highest content in the herb, whereas anemoside A3 displayed quite limited exposure. The hepatic first-pass effects were 71% for 23-hydroxybetulinic acid, 27% for anemoside B4 and 37% for anemoside A3, corresponding to their different extents of liver distribution. To our knowledge, this is the first investigation on the liver first-pass effect and distribution of P. chinensis saponins to date. These results also provide valuable information for the understanding of the pharmacological effect of P. chinensis saponins on liver diseases.

“…However, the evaluation of herbal pharmacokinetics is essential for the measurement of marker compounds. For a given dose of any herbal medicine, its physiological effect (or that of its constituents) is governed by the effective tissue concentration of the medicine, which in turn is determined by pharmacokinetic parameters, that is, the absorption, distribution, metabolism, and excretion of its various components . Knowledge regarding herbal pharmacokinetics may provide valuable information to aid practitioners in prescribing herbs safely and effectively.…”

Section: Discussionmentioning

confidence: 99%

“…For a given dose of any herbal medicine, its physiological effect (or that of its constituents) is governed by the effective tissue concentration of the medicine, which in turn is determined by pharmacokinetic parameters, that is, the absorption, distribution, metabolism, and excretion of its various components. 27 Knowledge regarding herbal pharmacokinetics may provide valuable information to aid practitioners in prescribing herbs safely and effectively. It may also enable useful predictions to be made, for example, regarding possible interactions between herbal remedies and conventional pharmaceuticals.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Safety of DW1029M, a Botanical Drug for the Treatment of Diabetic Nephropathy, Following Single Doses in Healthy Subjects

Jeon

Clinical Pharm in Drug Dev

et al. 2017

DW1029M is a botanical extract of Morus albalinne root bark and Puerariae radix that is used for the treatment of diabetic nephropathy. This study evaluated the safety and pharmacokinetics of DW1029M following its administration in healthy Korean subjects. We conducted a randomized, open-label, single-dose, crossover phase 1 clinical study. During each period, subjects received 300, 600, or 1200 mg oral doses of DW1029M. Plasma concentrations of puerarin, daidzin, and daidzein were analyzed using a liquid chromatography-tandem mass spectrometry. Six healthy male subjects completed the study. The maximum concentration of the drug in the plasma (C ) and area under the plasma drug concentration-time curve to the last measurable concentration (AUC ) for puerarin, daidzin, and daidzein were assessed after oral administration of DW1029M. No serious adverse events or clinically or statistically significant adverse events associated with any of the drug levels were observed. The results of the measurement of vital signs, electrocardiogram, laboratory tests, and physical examinations indicated that no clinically significant changes occurred during this study. The DW1029M tablet was safe and well tolerated over a single dose range of 300-1200 mg. This pharmacokinetic study of a botanical drug may aid in the development of DW1029M.