TY - JOUR
T1 - Evaluation of the pharmacokinetics and renal excretion of Ma-Zi-Ren-Wan in health subjects
AU - Hu, Dong Dong
AU - ZHONG, Lidan
AU - Wai, Kun
AU - Mu, Huai Xue
AU - Lin, Cheng Yuan
AU - Zhao, Ling
AU - Dai, Liang
AU - Huang, Tao
AU - BIAN, Zhaoxiang
N1 - Funding Information:
This work was supported by Hong Kong Baptist University Faculty Research Grant Category II. Grant No.: HKBU/ FRG2/13-14/025 and Shenzhen Science and Technology Innovation Committee JCYJ20140419130444178. Neither the funding agency nor any outside organization had a role in study design or manuscript preparation. This is not a commercial sponsored study. Zhao-Xiang Bian is the corresponding author and designed the study. Linda Li-Dan Zhong and Kun Wai drafted the protocol and enrolled the participants. Dong-Dong Hu and Ling Zhao collected the biological samples. Dong-Dong Hu and Huai-Xue Mu pretreated the plasma and urine samples. Dong-Dong Hu conducted the LC-MS/ MS analysis, data processing and drafted the manuscript. Linda Li-Dan Zhong, Kun Wai, Ling Zhao, Cheng-Yuan Lin, Tao Huang and Zhao-Xiang Bian revised the manuscript and gave critical advises. All authors read and approved the final manuscript. We thank Hong Kong Baptist University Faculty Research Grant Category II. Grant No.: HKBU/FRG2/13-14/025 for supporting this project. Special thanks to all the patients who participated in this study.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Background: Ma-Zi-Ren-Wan (MZRW) is a classic Chinese formula for treating human constipation. It is comprised of six herbs. Our previous studies have shown its great therapeutic effect. The absorbed compounds had been studied in rat, while there was no study about its components in human body. Objectives: To observe the components of MZRW absorbed in health subjects and study the pharmacokinetics of major compounds. At the same time, to observe the renal excretion of MZRW in health subjects based on the quantification of major compounds. Methods: Health adults were randomly assigned to three dose groups (5g, 7.5g and 10g q.d.) of MZRW. Blood samples were collected from the medial cubital vein just before and at 0.25, 0.5, 1, 2, 4, 8 and 12 h after administration. Urine samples were collected at 0 to 3 h, 3 to 6 h, 6 to 9 h and 9 to 12 h after MZRW administration, with the urine volume recorded for each time segment. Plasma and urine samples were analyzed by optimized LC-MSMS (Liquid chromatography-tandem mass spectrometry) method for pharmacokinetics and renal excretion study of MZRW. Results: Ten compounds of MZRW were observed in 23 health subjects. Due to the low concentration in plasma at the current dose, only four compounds (Albiflorin, paeoniflorin, magnolol and rhein) were quantified in the plasma sample. Honokiol, aloe emodin and emodin could only meet the LLOQ at some time points of the high dose group. Hesperidin, naringin and amygdalin could not be detected in plasma sample. While seven compounds (Amygdalin, albiflorin, paeoniflorin, magnolol, honokiol, rhein and aloe emodin) could be quantified in urine, the renal excretion was well studied. Conclusion: MZRW was safe and well tolerated in this clinical study. Albiflorin, paeoniflorin, magnolol and rhein was well quantified in plasma. The renal excretion of paeoniflorin, albiflorin and rhein were dose dependent for doses ranging between 5 and 10g.
AB - Background: Ma-Zi-Ren-Wan (MZRW) is a classic Chinese formula for treating human constipation. It is comprised of six herbs. Our previous studies have shown its great therapeutic effect. The absorbed compounds had been studied in rat, while there was no study about its components in human body. Objectives: To observe the components of MZRW absorbed in health subjects and study the pharmacokinetics of major compounds. At the same time, to observe the renal excretion of MZRW in health subjects based on the quantification of major compounds. Methods: Health adults were randomly assigned to three dose groups (5g, 7.5g and 10g q.d.) of MZRW. Blood samples were collected from the medial cubital vein just before and at 0.25, 0.5, 1, 2, 4, 8 and 12 h after administration. Urine samples were collected at 0 to 3 h, 3 to 6 h, 6 to 9 h and 9 to 12 h after MZRW administration, with the urine volume recorded for each time segment. Plasma and urine samples were analyzed by optimized LC-MSMS (Liquid chromatography-tandem mass spectrometry) method for pharmacokinetics and renal excretion study of MZRW. Results: Ten compounds of MZRW were observed in 23 health subjects. Due to the low concentration in plasma at the current dose, only four compounds (Albiflorin, paeoniflorin, magnolol and rhein) were quantified in the plasma sample. Honokiol, aloe emodin and emodin could only meet the LLOQ at some time points of the high dose group. Hesperidin, naringin and amygdalin could not be detected in plasma sample. While seven compounds (Amygdalin, albiflorin, paeoniflorin, magnolol, honokiol, rhein and aloe emodin) could be quantified in urine, the renal excretion was well studied. Conclusion: MZRW was safe and well tolerated in this clinical study. Albiflorin, paeoniflorin, magnolol and rhein was well quantified in plasma. The renal excretion of paeoniflorin, albiflorin and rhein were dose dependent for doses ranging between 5 and 10g.
KW - Human plasma
KW - LC-MS/MS
KW - Ma-Zi-Ren-Wan
KW - Pharmacokinetics
KW - Renal Excretion
UR - http://www.scopus.com/inward/record.url?scp=85044263481&partnerID=8YFLogxK
U2 - 10.15806/j.issn.2311-8571.2016.0050
DO - 10.15806/j.issn.2311-8571.2016.0050
M3 - Journal article
AN - SCOPUS:85044263481
SN - 2311-8571
VL - 3
SP - 8
EP - 15
JO - World Journal of Traditional Chinese Medicine
JF - World Journal of Traditional Chinese Medicine
IS - 2
ER -
