Pilot study of the uricosuric effect of DuP-753, a new angiotensin II receptor antagonist, in healthy subjects.
The uricosuric effect of DuP-753, a novel, specific angiotensin II receptor antagonist, has been explored in a healthy male Japanese volunteers, given single oral doses of 25, 50, 100 or 200 mg (n = 6), or 100 mg (n = 6) or placebo (n = 3) once daily for 7 consecutive days. In the single-dose study, serum uric acid measured at 4 h after dosing showed a dose dependent decrease; the reductions from the corresponding pre-dose values were: 0.32 (25 mg), 0.77 (50 mg), 1.25 (100 mg) and 1.33 mg.dl-1 (200 mg). The urinary excretion of uric acid within the first 4 h after treatment was also increased in a dose-dependent manner, whereas the urinary excretion of creatinine remained unchanged. In the multiple-dose study, DuP-753 significantly decreased the serum uric acid concentration measured 4 h both after the first (pre-dose value: 5.68 vs 4 h after: 4.48 mg.dl-1) and last administrations (4.42 mg.dl-1). Simultaneously, the ratio of urinary uric acid to creatinine excretion was significantly increased within the first 4 h both after the first (DuP-753: 1.190 vs placebo: 0.576) and last administrations (1.02 vs 0.576). The findings suggest that DuP-753 possesses a uricosuric effect both after single and multiple doses in healthy subjects. The effect should be further examined in hypertensive patients.
Nakashima
M
M
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Uematsu
T
T
Kosuge
K
K
Kanamaru
M
M
D000328:Adult; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds / Q000494:pharmacology*; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D019808:Losartan; D008297:Male; D010865:Pilot Projects; D012016:Reference Values; D013777:Tetrazoles / Q000494:pharmacology*; D014527:Uric Acid / Q000378:metabolism*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D014527:Uric Acid; D003404:Creatinine; D019808:Losartan