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Kavitha G. Shekar, 21 Jun 2016

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UA-lowering with febuxostat, benzbromarone effective in hypertensive patients

15 Mar 2017

Uricosuric drugs show therapeutic potential in the management of patients with hypertension and hyperuricemia, providing greater improvements in vascular function compared with uric acid (UA) synthesis inhibitors, according to a study.

A total of 20 hypertensive patients (mean age 64 years; 90 percent male) with inadequate UA control was included in the study, which consisted of three phases. Phase I involved randomization to febuxostat 40 mg (Feb) or benzbromarone 50 mg (Ben) once daily for 3 months, phase II involved administration of a combination of the previous drugs but at lower doses (Feb 20 mg/Ben 25 mg) for another 3 months, and phase III facilitated administration of either Feb or Ben once daily for 3 months in a modified crossover manner.

UA metabolism was evaluated by measuring UA excretion and clearance from blood and urine samples, whereas blood pressure (BP) measurements were taken while seated at a doctor’s office. All assessments were performed at baseline and at the end of each treatment period. Indices of organ damage were also examined.

The 9-month data showed no significant changes in BP or estimated glomerular filtration rate (eGFR) following treatment with each UA-lowering regimen. However, substantially greater changes were observed in UA with Feb/Ben than with Feb alone, as well as in UA excretion and clearance with Ben than with Feb and Feb/Ben. Other differences observed were in urinary 8-hydroxydeoxyguanosine and liver-type fatty-acid-binding protein levels which were slightly lower with Ben, and in flow-mediated dilation which was slightly higher with Feb/Ben and Ben.

Researchers noted that the low-dose combination of the UA synthesis inhibitor and uricosuric agent had greater UA-lowering effects compared with the standard dose of each agent alone. The underlying mechanism for this effect might involve xanthine oxidase (XO), an enzyme responsible for the production of UA.

“Activation of vascular XO represents an early mechanism that contributes to increased radical formation and endothelial dysfunction in the atherosclerotic disease process,” they explained.

While UA synthesis inhibitors (ie, febuxostat) inhibit the XO system and decrease oxidative stress generated during the production of UA, uricosuric agents (ie, benzbromarone) do not exert an effect on the XO pathway but has been shown to improve inflammatory markers and insulin resistance.

“Thus, combination therapy of these two drugs seems to clarify the organ-protective effects through the different mechanisms and may have been due to the different sites of action and synergistic effects,” although long-term observations about cardiovascular events may be necessary, they said.

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Most Read Articles
01 Oct 2015
BLACKMORES VITAMIN D3 – Vitamin D3 1,000 IU Capsules
15 Dec 2016
New drug applications approved by US FDA as of 1 - 15 December 2016 which includes New Molecular Entities (NMEs) and new biologics. It does not include Tentative Approvals. Supplemental approvals may have occurred since the original approval date.
Kavitha G. Shekar, 21 Jun 2016

The American Diabetes Association’s (ADA) President Desmond Schatz challenged the scientific community to transform diabetes from an invisible disease to a highly visible crisis. “Diabetes is an epidemic spiralling out of control across this country and around the world, yet it remains largely invisible,” he said, speaking at the 76th Scientific Sessions of ADA in New Orleans, Louisiana, US.

31 Jul 2017
New drug applications approved by US FDA as of 16 - 31 July 2017 which includes New Molecular Entities (NMEs) and new biologics. It does not include Tentative Approvals. Supplemental approvals may have occurred since the original approval date.