Drug Interaction Study of Olmesartan in Healthy Chinese Volunteers

July 24, 2013 updated by: Kunyan Li, Central South University

Effect of Probenecid on Pharmacokinetics, and Tolerability of Olmesartan in Healthy Chinese Volunteers

Hypertension and hyperuricaemia are widespread conditions. There is significant overlap between the two conditions. Serum uric acid (SUA) is currently recognized as a risk factor for cardiovascular disease. Thus, at some point in their therapy, hypertensive patients with hyperuricaemia are likely to require concurrent treatment with anti-hypertensive and hypouricaemic agents. For this reason, it is important to determine whether there are any pharmacokinetic interactions resulting from the concomitant administration of such agents.Olmesartan is an angiotensin II receptor antagonist and effective and well tolerated in the treatment of arterial hypertension. Probenecid is a well-established hypouricaemic agent for the treatment of hyperuricaemia and gout.The goal of this study was to examine the impact of coadministration of probenecid on the pharmacokinetic parameters and tolerability of olmesartan in healthy volunteers.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Probenecid is a well-established hypouricaemic agent for the treatment of hyperuricaemia and gout and is thought to act on urate transporter 1 (URAT1), a novel member of the organic anion transporter (OAT) family, thereby increasing uric acid excretion in the kidney by blocking urate reuptake, and then, resulting in a decrease of SUA.

Olmesartan is an angiotensin II receptor antagonist and effective and well tolerated in the treatment of arterial hypertension. Olmesartan is orally administered in the prodrug form, olmesartan medoxomil, which is converted to the pharmacologically-active compound olmesartan upon de-esterification by the enzyme arylesterase in the intestinal wall, portal blood, and liver. Olmesartan is excreted by hepatobiliary and renal systems without further metabolism, and its pharmacokinetic profile is not affected by age or gender. In addition, the pharmacokinetic and pharmacodynamic profile of olmesartan is favorable, both in terms of providing effective 24-hour blood pressure (BP) control with once-daily dosing, and in restricting the likelihood of pharmacokinetic interactions with other drugs. Studies in vitro show organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, multidrug resistance-associated protein 2 (MRP 2), and breast cancer resistance protein (BCRP) are involved in hepatobiliary and renal transport of olmesartan. We know probenecid interferes with the kidneys' organic anion transporter (OAT). Will probenecid have effects on the pharmacokinetics of olmesartan thereby result in changes of antihypertensive effect and side effects of olmesartan? Until now, many clinical studies have shown olmesartan has no pharmacokinetic interactions with other drugs; moreover, there is no research about the interactions between olmesartan and probenecid. In this study, we assess the involvement of probenecid in the pharmacokinetics and tolerability of olmesartan.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Hunan
      • Changsha, Hunan, China, 410006
        • Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital (The Affiliated Tumor Hospital of Xiangya Medical School of Central South University)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • written informed consent obtained,
  • age 18 to 40 years and a body mass index between 19 and 25 kg/m2;
  • negative test results for HIV and hepatitis В and C non-smoking status and
  • an unremarkable clinical history

Exclusion Criteria:

  • has history or evidence of a renal, gastrointestinal, hepatic, or hematologic abnormality or
  • any acute or chronic disease, or
  • an allergy to any drugs

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: olmesartan medoxomil, PK of olmesartan
drug: olmesartan medoxomil; dosage form: oral tablet; dosage: 20mg/time; frequency: once a day; duration: 4 days
Drug: olmesartan medoxomil
Other Names:
  • BENICAR
  • CS-866
Experimental: olmesartan medoxomil+probenecid, PK of olmesartan
drug1: olmesartan medoxomil; dosage form: oral tablet; dosage: 20mg/time; frequency: once a day; duration: 4 days; drug2: probenecid; dosage form: oral tablet; dosage: 500mg/time; frequency: 2 times/day; duration: 1 day
Drug: olmesartan medoxomil+probenecid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
pharmacokinetic parameters
Time Frame: 48 hours after last administration of olmesartan medoxomil
pharmacokinetic parameters:AUC0-48, AUC0→∞ and Css-av , tmax, t1/2, Css-max, and Css-min
48 hours after last administration of olmesartan medoxomil

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
vital signs
Time Frame: at baseline (0) and at 1, 2, 3, 6, 12, 36, and 48 hours after last dosage of olmesartan medoxomil administration
vital signs: blood pressure, heart rate, and respiratory rate
at baseline (0) and at 1, 2, 3, 6, 12, 36, and 48 hours after last dosage of olmesartan medoxomil administration

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Laboratory tests
Time Frame: at baseline and after completion of the study during 48 hours
biochemistry and hematology test, routine urine test
at baseline and after completion of the study during 48 hours
electrocardiography
Time Frame: at baseline and after completion of the study during 48 hours
at baseline and after completion of the study during 48 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Central South University

Investigators

  • Principal Investigator: Kunyan Li, phD, Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital (The Affiliated Tumor Hospital of Xiangya Medical School of Central South University)
  • Study Director: Nong Yang, MS, Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital (The Affiliated Tumor Hospital of Xiangya Medical School of Central South University)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2009

Primary Completion (Actual)

September 1, 2009

Study Completion (Actual)

October 1, 2009

Study Registration Dates

First Submitted

July 22, 2013

First Submitted That Met QC Criteria

July 24, 2013

First Posted (Estimate)

July 25, 2013

Study Record Updates

Last Update Posted (Estimate)

July 25, 2013

Last Update Submitted That Met QC Criteria

July 24, 2013

Last Verified

July 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 200704

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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