Pharmacokinetics of nebivolol and ramipril are not affected by co-administration

Background The unique antihypertensive action of nebivolol (N) is believed to be due to combined β1-receptor antagonism and endothelial nitric oxide releasing capabilities which have been reported to improve hemodynamics and left ventricular function. ACE inhibitors are often used with β-blockers in cardiovascular therapy. Thus, co-administration of N and ramipril (R) was assessed for pharmacokinetic (PK) interaction. Methods Healthy subjects[12 extensive (EM), 3 poor (PM) metabolizers, from CYP2D6 genotype] in this open-label, randomized, two parallel group study received oral N (10 mg QD) or R (5 mg QD) on Days 1–10 or 21–30. On Days 11–20, oral R plus N were given. Blood was taken on Days 10, 20, 30 and prior to the 8th and 9th doses of each phase. Plasma d- and l-N and/or R and ramiprilat (Rlat) levels were measured by LC/MS. PK parameter estimates were statistically compared using 90% confidence intervals (CIs). Results (see Table) No clinically relevant changes in the PK of d-N or l-N enantiomers were noted and R data were at the assay's LOQ. Conclusion Co-administration of N and R did not appear to affect the clinical PK profile of either antihypertensive agent. Clinical Pharmacology & Therapeutics (2005) 77, P77–P77; doi: 10.1016/j.clpt.2004.12.186 Cpeak AUCt Analyte Ratio 90%CI Ratio 90%CI EM-d,l-N (n = 12) 0.96 0.78–1.18 0.97 0.92–1.02 PM-d,l-N (n = 3) 0.90 0.75–1.07 0.93 0.87–1.00 Rlat (n = 15) 1.03 0.98–1.09 1.02 0.99–1.05