Effects of a fenofibrate/losartan combination on the plasma concentration and urinary excretion of purine bases.
OBJECTIVE
To assess the effects of a combination of fenofibrate and losartan on the plasma concentrations and urinary excretion of purine bases in healthy male subjects.


METHODS
5 healthy males participated in a fenofibrate plus losartan combination study. The plasma concentrations and urinary excretion of purine bases (hypoxanthine, xanthine, uric acid) were measured before and after administrations of losartan (100 mg o.d.) alone for 2 weeks, losartan and fenofibrate together for 2 weeks and fenofibrate (300 mg o.d.) alone for 2 weeks, which were given consecutively over a 6-week period.


RESULTS
Losartan alone significantly reduced the serum uric acid concentration and increased uric acid excretion, whereas the combination of losartan and fenofibrate reduced serum uric acid concentrations further with a concomitant increased uric acid excretion. Fenofibrate alone also reduced plasma uric acid concentration with an increase in urinary excretion, although the effect was weak when compared with the combination treatment. The plasma concentrations and urinary excretion of oxypurines remained unchanged throughout the entire study.


CONCLUSIONS
A combination of fenofibrate and losartan demonstrated an additive urate-lowering effect which may be beneficial in the treatment of patients with gout and hypertriglyceridemia.
Ka
T
T
Division of Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Inokuchi
T
T
Tsutsumi
Z
Z
Takahashi
S
S
Moriwaki
Y
Y
Yamamoto
T
T
D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D011345:Fenofibrate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D019271:Hypoxanthine / Q000097:blood / Q000652:urine; D019808:Losartan / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014527:Uric Acid / Q000097:blood* / Q000652:urine*; D019820:Xanthine / Q000097:blood / Q000652:urine
D000959:Antihypertensive Agents; D000960:Hypolipidemic Agents; D014280:Triglycerides; D019820:Xanthine; D014527:Uric Acid; D019271:Hypoxanthine; D002784:Cholesterol; D019808:Losartan; D011345:Fenofibrate