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Effect of chronic administration of fluoxetine on the pharmacokinetics of nebivolol
Author(s) -
Shaw A. A.,
Liu S.,
Zachwieja L. F.,
Donnelly C. M.,
Huang M. Y.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.038
Subject(s) - cmax , nebivolol , pharmacology , pharmacokinetics , cyp2d6 , chemistry , oral administration , dextromethorphan , medicine , enzyme , cytochrome p450 , biochemistry , blood pressure
Background Nebivolol (N) is considered a unique racemic cardio‐selective β 1 ‐antagonist with vascular endothelial nitric oxide modulating capabilities that undergoes extensive metabolism to active moieties via the CYP2D6 enzymatic pathway. Fluoxetine (F), one of the most studied potent inhibitors and substrates of CYP2D6 enzyme used clinically, was selected to assess the potential interactions with N. Methods Ten CYP2D6 extensive metabolizers (EM) received an oral 10 mg dose of N on Day 1, an oral 20 mg dose of F QD on Days 8 through 27, and 10 mg N plus 20 mg F on Day 28. PK estimates for N were assessed. Results (see Table) Co‐administration of N with F was well tolerated. Conclusions The results confirm N's reliance on the CYP2D6 enzymatic pathway for elimination. The elevated N plasma concentrations seen with the co‐administration of F were considerably lower than the clinically safe and well‐tolerated levels of N alone previously observed in poor metabolizer subjects (AUC ∞ : 614 ng·hr/mL; C max : 9.21 ng/mL). Clinical Pharmacology & Therapeutics (2005) 77 , P38–P38; doi: 10.1016/j.clpt.2004.12.038Parameter Day 1 Day 28 Ratio 90% CIAUC ∞ (ng hr/mL) 13.87 92.33 6.02 4.57–7.91 C max (ng/mL) 2.33 5.45 2.27 1.83–2.80 T max (hr) 1.30 2.60 2.00 1.58–2.42 t 1/2 (hr) 12.51 17.45 1.40 1.07–1.72 Cl/F (L/hr) 787.0 142.9 0.18 0.014–0.35