Evaluation of the pharmacokinetics and renal excretion of Ma-Zi-Ren-Wan in health subjects

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.