The Interaction of Herbs and Statins

Interactions of Herbs With Statin Drugs and Potential Mediation by Drug Transporters

This project includes two separate pharmacokinetic studies with simvastatin and rosuvastatin, respectively. Each study is an open-label, single-dose, randomized, three-phase (no herbs, with green tea, with soy isoflavones) clinical pharmacokinetic study design with a wash-out of at least 4-weeks between phases. The aim is to examine whether green tea extract and soy isoflavones affect the pharmacokinetics of simvastatin and rosuvastatin in healthy subjects and whether these interactions are influenced by polymorphisms in the relevant drug transporters, solute carrier 1B1 (SLCO1B1) and adenosine triphosphate (ATP) binding cassette G2 (ABCG2) and to identify whether polymorphisms in drug transporters influence the pharmacokinetics of simvastatin and rosuvastatin. After informed consent is obtained, subjects are required to abstain from any prescription or non-prescription medications 2 weeks before and throughout the study. Subjects are given a single dose of simvastatin 20 mg (Zocor®, MSD) or rosuvastatin 10 mg (Crestor®, Astra Zeneca) on 3 occasions: 1. without herbs; 2. with green tea extract; 3. with soy isoflavones extract. The green tea extract and soy isoflavones extract are given at a dose containing epigallocatechin gallate (EGCG) 800 mg once daily or isoflavones 120 mg once daily for 14 days before statin dosing with at least 4-week washout period between phases. Blood samples are taken at intervals from 0 to 24 hours on the statin dosing days. During the study, subjects are reminded frequently of the requirements on diet.

Study Overview

• Status: Completed
• Conditions: Drug Interaction
• Intervention / Treatment: Drug: Simvastatin 20 mg (Zocor®, MSD); Drug: rosuvastatin 10 mg (Crestor®, Astra Zeneca)

Detailed Description

Healthy Chinese male subjects aged 18-45 years are recruited from a pool of over 200 healthy volunteers who had been genotyped for the SLCO1B1 388A>G, 521T>C and ABCG2 421C>A polymorphisms. All subjects are required to abstain from any prescription or non-prescription medications 2 weeks before and throughout the study. They are not allowed to take alcohol, tea, grapefruit juice, caffeine, soybean milk or dietary supplements and herbal products 2 weeks before and throughout the entire study period. They are also not allowed to smoke 2 weeks before and throughout the study. Subjects are requested to fast for 10 h before and 4 h after drug administration during the blood sampling sessions. Meals are standardized and consumed at 4 h and 10 h post dosing. Drinking water are not allowed from 1 h pre-dose to 1 h post-dose except that needed for drug dosing at the time of blood sampling sessions. Subjects are given a single dose of simvastatin 20 mg (Zocor®, MSD) or rosuvastatin 10 mg (Crestor®, Astra Zeneca) on 3 occasions: 1. without herbs; 2. with green tea extract; 3. with soy isoflavones extract. The green tea extract and soy isoflavones extract are given at a dose containing EGCG 800 mg once daily or isoflavones 120 mg once daily for 14 days before statin dosing with at least 4-week washout period between phases.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 4

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Chinese University of Hong Kong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy Chinese male subjects aged 18 - 45 years
• healthy volunteers who had been genotyped for the SLCO1B1 388A>G, 521T>C and ABCG2 421C>A polymorphisms.

Exclusion Criteria:

• Female
• Patients with any disease
• Volunteers who cannot follow the instructions
• Volunteers who don't sign the informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: simvastatin 20 mg (Zocor®, MSD); simvastatin 20 mg are given on 3 occasions: 1. without herbs; 2. with green tea extract containing EGCG 800 mg once daily for 14 days before statin dosing; 3. with soy isoflavones extract containing isoflavones 120 mg once daily for 14 days before statin dosing, with at least 4-week washout period between phases.	Drug: Simvastatin 20 mg (Zocor®, MSD); Simvastatin 20 mg given once alone, once with green tea extract and once with soy isoflavones extract.; Other Names: Green tea extract; Soy isoflavones extract
Other: rosuvastatin 10 mg (Crestor®, Astra Zeneca); rosuvastatin 10 mg are given on 3 occasions: 1. without herbs; 2. with green tea extract containing EGCG 800 mg once daily for 14 days before statin dosing; 3. with soy isoflavones extract containing isoflavones 120 mg once daily for 14 days before statin dosing, with at least 4-week washout period between phases	Drug: rosuvastatin 10 mg (Crestor®, Astra Zeneca); rosuvastatin 10 mg are given once alone, once with green tea extract and once with soy isoflavones extract.; Other Names: Green tea extract; Soy isoflavones extract

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The interactions of green tea extract and soy isoflavones on the maximum plasma concentration of simvastatin	Maximum plasma concentration for simvastatin comparing: 1. without herbs; 2. with green tea extract; 3. with soy isoflavones extract.	14 weeks
The interactions of green tea extract and soy isoflavones on the area under plasma concentration-time curve of simvastatin	Area under plasma concentration-time curve for simvastatin comparing: 1. without herbs; 2. with green tea extract; 3. with soy isoflavones extract.	14 weeks
The interactions of green tea extract and soy isoflavones on the maximum plasma concentration of rosuvastatin	Maximum plasma concentration for rosuvastatin comparing: 1. without herbs; 2. with green tea extract; 3. with soy isoflavones extract.	14 weeks
The interactions of green tea extract and soy isoflavones on the area under plasma concentration-time curve of rosuvastatin	Area under plasma concentration-time curve for rosuvastatin comparing: 1. without herbs; 2. with green tea extract; 3. with soy isoflavones extract.	14 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The influence of polymorphisms in drug transporters on the maximum plasma concentration of simvastatin and the interaction with herbs.	Maximum plasma concentration for simvastatin comparing: 1. without herbs; 2. with green tea extract; 3. with soy isoflavones extract with subjects divided according to genotypes of drug transporters.	14 weeks
The influence of polymorphisms in drug transporters on the area under plasma concentration-time curve of simvastatin and the interaction with herbs.	Area under plasma concentration-time curve for simvastatin comparing: 1. without herbs; 2. with green tea extract; 3. with soy isoflavones extract with subjects divided according to genotypes of drug transporters.	14 weeks
The influence of polymorphisms in drug transporters on the maximum plasma concentration of rosuvastatin and the interaction with herbs.	Maximum plasma concentration for rosuvastatin comparing: 1. without herbs; 2. with green tea extract; 3. with soy isoflavones extract with subjects divided according to genotypes of drug transporters.	14 weeks
The influence of polymorphisms in drug transporters on the area under plasma concentration-time curve of rosuvastatin and the interaction with herbs.	Area under plasma concentration-time curve for rosuvastatin comparing: 1. without herbs; 2. with green tea extract; 3. with soy isoflavones extract with subjects divided according to genotypes of drug transporters.	14 weeks

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2013
• Primary Completion (Actual): December 30, 2013
• Study Completion (Actual): August 28, 2021

Study Registration Dates

• First Submitted: August 29, 2021
• First Submitted That Met QC Criteria: September 30, 2021
• First Posted (Actual): October 8, 2021

Study Record Updates

• Last Update Posted (Actual): October 8, 2021
• Last Update Submitted That Met QC Criteria: September 30, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Statins
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Simvastatin
• Other Study ID Numbers: herbals

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No