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No effect of concomitant administration of nebivolol and losartan in healthy volunteers genotyped for CYP2D6 status
Author(s) -
Lawrence T. E.,
Chien C.,
Tu H. C.,
Phillips J. M.,
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.2004.12.206
Subject(s) - nebivolol , cyp2c9 , cmax , cyp2d6 , losartan , active metabolite , pharmacokinetics , medicine , pharmacology , metabolite , concomitant , clinical pharmacology , antagonist , metabolism , cytochrome p450 , angiotensin ii , blood pressure , receptor
Background Nebivolol (N) has been shown through a number of studies to be a cardioselective β 1 ‐antagonist with vascular endothelial nitric oxide releasing capabilities that exhibits CYP2D6‐mediated polymorphic metabolism. Losartan (L), an ARB, is extensively metabolized by CYP2C9 (a known polymorphic enzyme) and is likely to be used concomitantly. This study examined if co‐administration of N and L alters the pharmacokinetic (PK) characteristics of either agent, or the active metabolite of L, EXP‐3174. Methods This open‐label study was conducted in 24 subjects, genotyped for CYP2D6 status (EM n=20; PM n=4). Using a two‐sequence, two‐treatment design, single doses of 10 mg N (Day 1 or 29), 50 mg L (Day 1 or 29), or their combination (Day 15) were given. Blood samples for PK assessment were taken on Days 1, 15 and 29. Results (see Table) Conclusion There were no clinically meaningful changes observed in the PK of either L or N, confirming that the two agents should be capable of being safely co‐administered. Clinical Pharmacology & Therapeutics (2005) 77 , P82–P82; doi: 10.1016/j.clpt.2004.12.206C max AUC 0‐∞Parameter Ratio 90% CI Ratio 90% CIEM‐N 0.80 0.68–0.93 0.89 0.82–0.97 PM‐N 0.93 0.76–1.14 0.94 0.68–1.29 L 0.89 0.77–1.02 0.86 0.81–0.92 EXP‐3174 0.94 0.86–1.03 0.98 0.94–1.02