ClinicalTrials.gov
ClinicalTrials.gov Menu

Drug Interaction Study of Olmesartan in Healthy Chinese Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01907373
Recruitment Status : Completed
First Posted : July 25, 2013
Last Update Posted : July 25, 2013
Sponsor:
Information provided by (Responsible Party):
Kunyan Li, Central South University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Drug Interaction of Olmesartan in Healthy Chinese Volunteers Drug: olmesartan medoxomil Drug: olmesartan medoxomil+probenecid Phase 4

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  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Probenecid on Pharmacokinetics, and Tolerability of Olmesartan in Healthy Chinese Volunteers
Study Start Date : August 2009
Actual Primary Completion Date : September 2009
Actual Study Completion Date : October 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions

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



Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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


Other Outcome Measures:
  1. Laboratory tests [ Time Frame: at baseline and after completion of the study during 48 hours ]
    biochemistry and hematology test, routine urine test

  2. electrocardiography [ Time Frame: at baseline and after completion of the study during 48 hours ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01907373


Locations
China, Hunan
Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital (The Affiliated Tumor Hospital of Xiangya Medical School of Central South University)
Changsha, Hunan, China, 410006
Sponsors and Collaborators
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 automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kunyan Li, Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital (The Affiliated Tumor Hospital of Xiangya Medical School of Central South University), Central South University
ClinicalTrials.gov Identifier: NCT01907373     History of Changes
Other Study ID Numbers: 200704
First Posted: July 25, 2013    Key Record Dates
Last Update Posted: July 25, 2013
Last Verified: July 2013

Keywords provided by Kunyan Li, Central South University:
olmesartan
probenecid
pharmacokinetics
tolerability

Additional relevant MeSH terms:
Olmesartan
Olmesartan Medoxomil
Probenecid
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Uricosuric Agents
Gout Suppressants
Antirheumatic Agents
Renal Agents