Effect of silymarin pretreatment on the bioavailability of domperidone in healthy human volunteers
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Shravan Kumar Yamsani
Abstract
Background: The aim of this study was to investigate the effect of silymarin pretreatment on domperidone oral bioavailability in humans.
Methods: The rats were pretreated with silymarin for 7 days. The transport of domperidone across the rat intestine (duodenum, jejunum, ileum, and colon) was studied by using in vitro everted and non-everted sac methods. Samples were collected at preset time points and replaced with buffer. The drug content in the samples was estimated. The first part of the study included oral administration of 10 mg domperidone tablet alone, and blood was sampled from the antecubital vein. The second part of the study was conducted after a washout period of 2 weeks. Five hundred milligrams of silymarin was administered twice daily for 6 days. On day 7, one tablet each of 10 mg domperidone and 500 mg silymarin were administered concomitantly.
Results: In the everted sac and non-everted sac study with silymarin pretreatment, domperidone transport increased from the duodenum, jejunum, ileum, and colon. The silymarin pretreatment increased the bioavailability of domperidone. There was a statistically significant difference in the pharmacokinetic parameters Cmax,
Conclusions: The significant difference in absorption of domperidone on pretreatment with silymarin is due to the inhibition of P-glycoprotein and CYP3A. Silymarin, which inhibits CYP3A4, should be contraindicated for domperidone.
Acknowledgments
The authors thank All India Council for Technical Education (AICTE), New Delhi, India, for sanctioning the Research Promotion Scheme project (F. No: 8023/BOR/RPS-151/2006-07).
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research support played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
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©2014 by De Gruyter
Artikel in diesem Heft
- Frontmatter
- Editorial
- CYP 2C19 and UDP-glucuronosyltransferases not only for drugs but also for endobiotics
- Review
- Molecular functionality of CYP2C9 polymorphisms and their influence on drug therapy
- Reviews in Population Pharmacogenomics
- Pharmacogenetics in Jewish populations
- Frequency of CYP450 enzyme gene polymorphisms in the Greek population: review of the literature, original findings and clinical significance
- Original Articles
- Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors
- Effect of silymarin pretreatment on the bioavailability of domperidone in healthy human volunteers
- In vitro inhibitory effects of herbal supplements on tamoxifen and irinotecan metabolism
- Acknowledgment
- Acknowledgment
Artikel in diesem Heft
- Frontmatter
- Editorial
- CYP 2C19 and UDP-glucuronosyltransferases not only for drugs but also for endobiotics
- Review
- Molecular functionality of CYP2C9 polymorphisms and their influence on drug therapy
- Reviews in Population Pharmacogenomics
- Pharmacogenetics in Jewish populations
- Frequency of CYP450 enzyme gene polymorphisms in the Greek population: review of the literature, original findings and clinical significance
- Original Articles
- Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors
- Effect of silymarin pretreatment on the bioavailability of domperidone in healthy human volunteers
- In vitro inhibitory effects of herbal supplements on tamoxifen and irinotecan metabolism
- Acknowledgment
- Acknowledgment
