Disease relevance of S-8666

• The results should aid the understanding of the utility of S-8666 as a new diuretic antihypertensive which does not cause hyperuricemia during therapy [1].

High impact information on S-8666

• Additive diuretic effect of S-8666 during furosemide-induced diuresis in rats [2].
• Total urinary urate recovery after S-8666 administration was higher after the microinjection of [14C]urate into early proximal tubule sites [3].
• Glomerular filtration rate was not changed by S-8666 [3].
• The binding of S-8666 and M-I enantiomers to BSA also showed stereoselectivity [R(+) less than S(-)].(ABSTRACT TRUNCATED AT 250 WORDS)[4]
• Stereoselective disposition of S-8666, a novel uricosuric antihypertensive diuretic, and its N-monodemethylated metabolite in a perfused rat liver preparation. Effect of protein binding on the kinetics of S-8666 [4].

Associations of S-8666 with other chemical compounds

• Although the major site of action of S-8666 has been proven by the in vitro microperfusion study to be the thick ascending limb of Henle's loop, clearance studies in the rat suggested that this drug has an additional thiazide-like action [5].
• Probenecid, tienilic acid and R-(+)-enantiomer of S-8666, which is the uricosuric component of a new uricosuric diuretic, decreased the (Tua/Pua)/(Tin/Pin) value in the distal and proximal tubules by inhibiting urate secretion in PZO-untreated rats [6].

Gene context of S-8666

• S-8666 was also uricosuric in rats not given urate oxidase inhibitor [7].

Analytical, diagnostic and therapeutic context of S-8666

• Renal action of a novel uricosuric diuretic, S-8666. I. Clearance and tubular microinjection studies in rats [3].
• Since large portions were recovered from the urine as unchanged S-8666 after intravenous injection, most excretion occurs via the kidney [8].
• The Tmax values for individual enantiomers of S-8666 in fasted male monkeys were 30 min after oral administration [8].
• During perfusion with 100 nmol/ml of racemic S-8666 not containing bovine serum albumin (BSA), the steady-state hepatic extraction ratio of R(+)-S-8666 was two times higher (0.65 +/- 0.08) than that of S(-)-S-8666 (0.34 +/- 0.08) [4].

References