Effects of varying degrees of renal impairment on the pharmacokinetic disposition of nebivolol

Background Nebivolol (N) is believed to be a unique cardiovascular agent studied worldwide for the treatment of HTN, CHF and other cardiovascular conditions owing to its vascular endothelial nitric oxide modulating capabilities and its highly selective β1-antagonism. It is extensively metabolized with <0.1% of unchanged nebivolol excreted in urine. The present study examined what effect, if any, renal impairment has on oral N or its separate enantiomers. Methods Twenty-one subjects were divided into 3 renal impairment categories (mild, moderate, severe) based upon either measured (24-hour urine collection) or calculated (by Cockroft-Gault equation) creatinine clearance. Four healthy subjects, matched for age, gender, weight, and smoking habit, were selected as a control group. Results N (5 mg) was well tolerated with Cmax and Tmax being comparable across renal function classifications. Similar results were seen for the enantiomers and the active nebivolol glucuronide metabolites. (see Table) Conclusions Since apparent clearance is significantly diminished in patients with severe renal impairment, dose adjustment may need to be considered, an unexpected finding given N's lack of renal excretion. Clinical Pharmacology & Therapeutics (2005) 77, P38–P38; doi: 10.1016/j.clpt.2004.12.037 Table 1.  Category AUC∞ (ng hr/mL) 90% CI Cl/F (L/hr) 90% CI Healthy (n = 4) 6.59 N/A 891 N/A Mild (n = 7) 4.55 0.34–1.47 1241 0.73–2.05 Mod. (n = 9) 11.28 0.70–3.07 738 0.17–1.49 Severe (n = 5) 23.36 1.22–5.92 416 0–1.17