Recent research has contributed to our better understanding of Gout being overwhelmingly (95%) due to under-excretion rather than over-production of uric acid, or more precisely: intestinal under-excretion with renal excretion overload.
As such, drug development is increasingly focused on improving uric acid excretion via the various renal and gut transporters. Lesinurad, recently approved for use in the USA and Europe, is one such drug. It inhibits the main renal transporter URAT1 (and OAT4 too), preventing reabsorption of uric acid at the proximal tubules.
But we have other such dedicated uricosuric agents in our armamentarium:
1) Probenecid inhibits URAT1, GLUT9, OAT1 & OAT3;
2) Benzbromarone blocks URAT1, GLUT9 & OAT1.
Then there are other drugs, many used to treat associated conditions like DM, hypertension and dyslipidaemia, have mild to moderate uricosuric properties too! For patients with such associated metabolic syndrome diseases, some drugs with such dual effects may be very suitable. More on these in subsequent posts.
For Gout patients who also have hypertension, LOSARTAN has a powerful uricosuric effect, with as much as 20% serum uric acid reduction.
It probably works through blocking URAT1 & GLUT9.
A more recent study suggests that Irbesartan has a similar benefit, but other better controlled studies (like this double blind crossover experiment) prove otherwise.
This is the study suggesting Irbesartan may be uricosuric. I disagree because:
1) this is a retrospective study using multiple regression analysis;
2) the effect size is small and clinically insignificant;
3) the effect was only present in those with high baseline serum uric acid level (>6mg%).
Thoroughly unimpressive. I'll stick with Losartan.
For those with Gout and high cholesterol, ATORVASTATIN is the only statin with a uricosuric effect.
It is not clear how it exerts its mild uricosuric effect, but may have to do with sodium co-transport systems since sodium levels also go down after drug administration.
FENOFIBRATE is also a weak URAT1 inhibitor.
Diabetics with Gout would benefit from the uricosuric effect of the entire class of Gliflozins, inhibitors of SLGT2 (prevents glucose reabsorption in the kidneys).
The effect is mediated indirectly through glycosuria.
Leflunomide, a drug commonly used in Rheumatoid Arthritis, has a uricosuric effect.
Given that it is also phosphate-wasting, it may act through the sodium-phosphate transporter, NPT1, which is a known uric acid exporter.