Key result
Nebivolol and losartan co-administration shows no clinically meaningful pharmacokinetic interactions.
Why the study?
Nebivolol exhibits CYP2D6-mediated polymorphic metabolism and losartan is extensively metabolized by CYP2C9; their pharmacokinetic interaction when co-administered was unknown.
Does co-administration of nebivolol and losartan alter the pharmacokinetic characteristics of either agent in healthy volunteers?
Does co-administration of nebivolol and losartan alter the pharmacokinetic characteristics of either agent in healthy volunteers?
Co-administration of nebivolol and losartan does not significantly alter the pharmacokinetics of either drug, suggesting they can be safely used together.
Answers are grounded in this paper and cite their sources.
No PK interaction observed with nebivolol-losartan co-administration; supports safe concurrent use but leaves open confirmation in larger patient populations.
Background Nebivolol (N) has been shown through a number of studies to be a cardioselective β1-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.2004.12.206 Cmax AUC0-∞ Parameter Ratio 90% CI Ratio 90% CI EM-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
No takes yet. Share an insight, caveat, or question.
Lawrence et al. (2005) studied Healthy volunteers (n=24). Nebivolol and Losartan co-administration vs. Nebivolol alone or Losartan alone was evaluated on Pharmacokinetic characteristics (Cmax and AUC0-∞). Co-administration of nebivolol and losartan resulted in no clinically meaningful changes in the pharmacokinetics of either agent, indicating they can be safely co-administered.
Synapse has enriched 10 related papers. Consider them for comparative context: