Pharmacokinetics and Pharmacodynamics of Bisoprolol in Rats with Bilateral Ureter Ligation-induced Renal Failure

• Published in: Drug metabolism and pharmacokinetics 2006-01, Vol.21 (5), p.389-394
• Main Authors: Tahara, Katsutoshi, Saigusa, Katsuya, Kagawa, Yuka, Taguchi, Masato, Hashimoto, Yukiya
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - etiology; Acute Kidney Injury - metabolism; Acute Kidney Injury - physiopathology; Adrenergic beta-Agonists - pharmacology; Adrenergic beta-Antagonists - administration & dosage; Adrenergic beta-Antagonists - pharmacokinetics; Adrenergic beta-Antagonists - pharmacology; Analysis of Variance; Animals; Aspartate Aminotransferases - blood; bilateral ureter ligation; bisoprolol; Bisoprolol - blood; Bisoprolol - pharmacokinetics; Bisoprolol - pharmacology; Blood Urea Nitrogen; Creatinine - blood; Disease Models, Animal; Heart Rate - drug effects; Infusions, Intravenous; Isoproterenol - pharmacology; Ligation - adverse effects; Male; Metabolic Clearance Rate; pharmacokineticsWdynamics; Rats; Rats, Wistar; renal failure; Ureter - surgery; β-blocking action
• ISSN: 1347-4367; 1880-0920
• DOI: 10.2133/dmpk.21.389

The effect of renal failure on the pharmacokinetics and pharmacodynamics of bisoprolol was investigated in bilateral ureter-ligated (BUL) rats. The blood bisoprolol concentrations following 30-min intravenous infusion at a rate of 60 μg/kg/min were higher in renal artery-occluded (RAO) rats than in control rats, and were higher in BUL rats than in RAO rats. Increased blood bisoprolol concentrations accompanied decreased mean systemic clearances: 50.7, 36.4, and 26.2 mL/min/kg in control, RAO, and BUL rats, respectively. The finding indicated that approximately 30% of administered bisoprolol was excreted via the kidney, and that not only the renal clearance but also non-renal clearance of bisoprolol was decreased in BUL rats. The β-blocking action of bisoprolol was assessed by the reduction in isoproterenol-induced increases in the heart rate. The relationship between blood concentration and the β-blocking action of bisoprolol in BUL rats was similar to that in control rats. These results suggested that renal excretion and hepatic metabolism of bisoprolol were significantly reduced in BUL rats, but that pharmacodynamics of bisoprolol was not altered by acute renal failure.