Lack of pharmacokinetic interaction between nebivolol and spironolactone

Background To detect interaction between nebivolol (N), a unique cardioselective β-blocker shown to possess vascular endothelial nitric oxide releasing capabilities, and spironolactone by comparing pharmacokinetic (PK) parameters for spironolactone (S) and metabolites, canrenone (C) and 7α-thiomethyl spirolactone (TMS), in healthy subjects. This potassium-sparing diuretic (S) is used with β-blockers to treat CHF. Previously, S showed no effect on the PK of N. Methods Thirty-six healthy subjects were enrolled, without regard to CYP2D6 genotype, in this open-label, randomized, one period study. Subjects received once-daily oral S (25 mg) on Days 1–10 and oral S (25 mg) plus N (10 mg) once-daily on Days 11–20. Blood samples were collected on Days 10 and 20 and prior to dosing on Days 8, 9, 18, and 19. Plasma concentrations of S, C and TMS were measured by LC/MS. Pharmacokinetic parameter estimates for S, C and TMS were compared by statistical analyses using 90% confidence intervals (CIs). Results All treatments were well tolerated. (see Table) Conclusion Co-administration of N (10 mg) with S (25 mg) results in no clinically significant changes in the PK profile of S, C or TMS. Clinical Pharmacology & Therapeutics (2005) 77, P46–P46; doi: 10.1016/j.clpt.2004.12.070 Cmax AUCT Analyte Ratio 90% CI Ratio 90% CI S 1.06 0.95–1.19 0.95 0.90–1.02 C 1.04 1.00–1.09 1.05 1.03–1.08 TMS 1.19 1.10–1.29 1.14 1.07–1.20