Antihypertensive activity and pharmacokinetics of KD3-671, a nonpeptide AT1-receptor antagonist, in renal hypertensive dogs

Journal of Cardiovascular Pharmacology
Y TakataH Kato

Abstract

The antihypertensive activity and pharmacokinetics of KD3-671 (previously named KT3-671), a nonpeptide AT1-receptor antagonist, were investigated in renal hypertensive dogs with normal or high plasma renin activity (PRA). A single administration of KD3-671 at 3 and 10 mg/kg, p.o., to the hypertensive dogs with high PRA dose-dependently reduced mean blood pressure (MBP), which was not correlated with plasma KD3-671 concentration. Significant increases in PRA and plasma angiotensin (Ang) II occurred 2 h after KD3-671 dosing. Enalapril at 3 mg/kg, p.o., also reduced MBP. Neither KD3-671 nor enalapril affected heart rate. When given orally once a day for 29 days to the hypertensive dogs with normal PRA, KD3-671 at 3 and 10 mg/kg/day dose-dependently reduced MBP, which was smaller than that in the dogs with high PRA. This was the case for enalapril. The hypotension induced by the first dose of KD3-671 or enalapril was consistently observed after doses 8, 15, 22, and 29. After cessation of repeated dosing, no rebound phenomenon in MBP was observed. Pharmacokinetic parameters of KD3-671 were not influenced by repeated dosing. KD3-671 markedly increased both PRA and plasma Ang II concentration at 2 h after dosing. These results suggest...Continue Reading

References

Jan 1, 1987·Clinical and Experimental Hypertension. Part A, Theory and Practice·M MiyazakiN Toda
Jan 1, 1973·Acta Endocrinologica. Supplementum·J NussbergerW Siegenthaler
May 1, 1972·Circulation Research·A N LupuF N White
Oct 1, 1993·Journal of Cardiovascular Pharmacology·G M OlinsS E Bittner
Jan 1, 1995·Journal of Cardiovascular Pharmacology·S MochizukiA Tomiyama
Jan 1, 1995·Hypertension·A H van den MeirackerA J Man In 't Veld
Jan 1, 1994·British Journal of Pharmacology·A HilditchM J Robertson
Nov 1, 1993·Japanese Journal of Pharmacology·K HamadaT Ono

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Citations

Aug 14, 2012·International Journal of Nephrology·Rory McQuillanCharmaine E Lok
Jun 17, 2003·Biological & Pharmaceutical Bulletin·Tadashi NagamatsuYoshio Suzuki
Dec 4, 2003·British Journal of Clinical Pharmacology·D PattersonT MacDonald
Jun 19, 2010·Journal of Veterinary Pharmacology and Therapeutics·M Martinez, S Modric

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