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 β 1 ‐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 8 th and 9 th 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.2004.12.186C peak AUC tAnalyte Ratio 90%CI Ratio 90%CIEM‐ 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