Nebivolol
Nebivolol. Third-generation β1-selective adrenergic blocker — also stimulates endothelial nitric oxide synthesis → vasodilation that other… Oral half-life 10 h.
Third-generation β1-selective adrenergic blocker — also stimulates endothelial nitric oxide synthesis → vasodilation that other β-blockers lack. Lower fatigue + sexual side-effect profile. CYP2D6 substrate; poor metabolizers have ~10× higher AUC.
PK: zero-content, and a population mismatch — its citation is a CHRONIC KIDNEY DISEASE and haemodialysis study reporting only enantiomer exposures. V 700 L is a rounding of a 673 L the cited paper never gives; the real figure is an intravenous-derived steady-state volume, so pairing it with a bioavailability is correct. A SINGLE SCALAR IS NOT DEFENSIBLE: steady-state concentrations are 10 to 15-fold greater in CYP2D6 poor metabolisers, clearance falls from 51.6 to 15-18 L/h and the half-life rises from 10.3 to 32-34 h, so this record should really be two phenotype rows. THE EFFECT IS DECOUPLED IN AN UNUSUAL DIRECTION: despite that 10 to 15-fold exposure difference, "EMs and PMs displayed similar BP responses", attributed to active hydroxylated metabolites — so the parent curve is not the effect driver in extensive metabolisers. ITS EFFECT-COMPARTMENT VALUE IS REMOVED: it was borrowed from a RAT S(-)-ATENOLOL study, and the "2.52" its note attributed to that paper does not appear there — it is a unit conversion of 0.042 per minute presented as the paper figure.
Pharmacokinetics
- Oral — t½ 10.3 h · F 12% · Vd 673 L
Sources: PMID:26914703, PMID:2462161, PMID:9112066, PMID:17094780