Tags

Type your tag names separated by a space and hit enter

An assessment of pharmacokinetics and antioxidant activity of free silymarin flavonolignans in healthy volunteers: a dose escalation study.
Drug Metab Dispos. 2013 Sep; 41(9):1679-85.DM

Abstract

Milk thistle (Silybum marianum) extracts, one of the most widely used dietary supplements, contain a mixture of six major flavonolignans (silybin A, silybin B, isosilybin A, isosilybin B, silychristin, and silydianin) and other components. However, the pharmacokinetics of the free individual flavonolignans have been only partially investigated in humans. Furthermore, antioxidant effects of the extract, which may underlie the basis of many therapeutic effects, have not been thoroughly assessed. The present study evaluated the pharmacokinetics of the six major flavonolignans in healthy volunteers receiving single doses of either one (175 mg), two (350 mg), or three (525 mg) milk thistle capsule(s) on three separate study visits. Additionally, the steady-state pharmacokinetic parameters were determined after the subjects were administered one capsule three times daily for 28 consecutive days. Our results demonstrated that all six flavonolignans were rapidly absorbed and eliminated. In order of abundance, the exposure to free flavonolignans was greatest for silybin A followed by silybin B, isosilybin B, isosilybin A, silychristin, and silydianin. The systemic exposure to these compounds appeared linear and dose proportional. The disposition of flavonolignans was stereoselective, as evidenced by the apparent clearance of silybin B, which was significantly greater than silybin A, whereas the apparent clearance of isosilybin B was significantly lower than isosilybin A. The concentrations of urinary 8-epi-prostaglandin F2α, a commonly used biomarker of oxidative status in humans, were considerably decreased in study subjects after a 28-day exposure to the extract (1.3 ± 0.9 versus 0.8 ± 0.9 ng/mg creatinine) but failed to reach statistical significance (P = 0.076).

Authors+Show Affiliations

Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, Florida, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

23835761

Citation

Zhu, Hao-Jie, et al. "An Assessment of Pharmacokinetics and Antioxidant Activity of Free Silymarin Flavonolignans in Healthy Volunteers: a Dose Escalation Study." Drug Metabolism and Disposition: the Biological Fate of Chemicals, vol. 41, no. 9, 2013, pp. 1679-85.
Zhu HJ, Brinda BJ, Chavin KD, et al. An assessment of pharmacokinetics and antioxidant activity of free silymarin flavonolignans in healthy volunteers: a dose escalation study. Drug Metab Dispos. 2013;41(9):1679-85.
Zhu, H. J., Brinda, B. J., Chavin, K. D., Bernstein, H. J., Patrick, K. S., & Markowitz, J. S. (2013). An assessment of pharmacokinetics and antioxidant activity of free silymarin flavonolignans in healthy volunteers: a dose escalation study. Drug Metabolism and Disposition: the Biological Fate of Chemicals, 41(9), 1679-85. https://doi.org/10.1124/dmd.113.052423
Zhu HJ, et al. An Assessment of Pharmacokinetics and Antioxidant Activity of Free Silymarin Flavonolignans in Healthy Volunteers: a Dose Escalation Study. Drug Metab Dispos. 2013;41(9):1679-85. PubMed PMID: 23835761.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An assessment of pharmacokinetics and antioxidant activity of free silymarin flavonolignans in healthy volunteers: a dose escalation study. AU - Zhu,Hao-Jie, AU - Brinda,Bryan J, AU - Chavin,Kenneth D, AU - Bernstein,Hilary J, AU - Patrick,Kennerly S, AU - Markowitz,John S, Y1 - 2013/07/08/ PY - 2013/7/10/entrez PY - 2013/7/10/pubmed PY - 2014/4/2/medline SP - 1679 EP - 85 JF - Drug metabolism and disposition: the biological fate of chemicals JO - Drug Metab. Dispos. VL - 41 IS - 9 N2 - Milk thistle (Silybum marianum) extracts, one of the most widely used dietary supplements, contain a mixture of six major flavonolignans (silybin A, silybin B, isosilybin A, isosilybin B, silychristin, and silydianin) and other components. However, the pharmacokinetics of the free individual flavonolignans have been only partially investigated in humans. Furthermore, antioxidant effects of the extract, which may underlie the basis of many therapeutic effects, have not been thoroughly assessed. The present study evaluated the pharmacokinetics of the six major flavonolignans in healthy volunteers receiving single doses of either one (175 mg), two (350 mg), or three (525 mg) milk thistle capsule(s) on three separate study visits. Additionally, the steady-state pharmacokinetic parameters were determined after the subjects were administered one capsule three times daily for 28 consecutive days. Our results demonstrated that all six flavonolignans were rapidly absorbed and eliminated. In order of abundance, the exposure to free flavonolignans was greatest for silybin A followed by silybin B, isosilybin B, isosilybin A, silychristin, and silydianin. The systemic exposure to these compounds appeared linear and dose proportional. The disposition of flavonolignans was stereoselective, as evidenced by the apparent clearance of silybin B, which was significantly greater than silybin A, whereas the apparent clearance of isosilybin B was significantly lower than isosilybin A. The concentrations of urinary 8-epi-prostaglandin F2α, a commonly used biomarker of oxidative status in humans, were considerably decreased in study subjects after a 28-day exposure to the extract (1.3 ± 0.9 versus 0.8 ± 0.9 ng/mg creatinine) but failed to reach statistical significance (P = 0.076). SN - 1521-009X UR - https://www.unboundmedicine.com/medline/citation/23835761/An_assessment_of_pharmacokinetics_and_antioxidant_activity_of_free_silymarin_flavonolignans_in_healthy_volunteers:_a_dose_escalation_study_ L2 - http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=23835761 DB - PRIME DP - Unbound Medicine ER -