Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital (The Affiliated Tumor Hospital of Xiangya Medical School of Central South University)
Changsha, Hunan, 410006, China
Completed
NCT Number: NCT01907373
Drug Interaction Study 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.
Completed
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Notify MeKey information
Age range
18 year–40 year
Sex eligibility
All sexes
Study type
Interventional
Phase
Phase 4
Primary location
About this study
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.
Who can participate
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
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
Treatment and study plan
olmesartan medoxomil
DrugOther names: BENICAR, CS-866
olmesartan medoxomil+probenecid
DrugPrimary outcomes
-
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 outcomes
-
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 outcomes
-
Laboratory tests
Time frame: at baseline and after completion of the study during 48 hours
biochemistry and hematology test, routine urine test
-
electrocardiography
Time frame: at baseline and after completion of the study during 48 hours
Sponsors and collaborators
Lead sponsor
Central South University
Other
Registry information
Official study title
Effect of Probenecid on Pharmacokinetics, and Tolerability of Olmesartan in Healthy Chinese Volunteers
Important dates
- Study start
- 2009
- Primary completion
- 2009
- Study completion
- 2009
- First posted
- Jul 25, 2013
- Registry last updated
- Jul 25, 2013
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.