Drug Interaction Study of Olmesartan in Healthy Chinese Volunteers
Condition: Drug Interaction of Olmesartan in Healthy Chinese Volunteers
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): olmesartan medoxomil; olmesartan medoxomil+probenecid
Intervention type(s): Drug; Drug
Other intervention name(s): BENICAR; CS-866
Intervention MeSH terms: Probenecid; Olmesartan; Olmesartan Medoxomil
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: olmesartan; probenecid; pharmacokinetics; tolerability