Revefenacin

China [CN]

I. Basic Information

Item | Details

English Name | Revefenacin

Chinese Name | Revefenacin (瑞维法新)

CAS Number | 864750-70-9

Chemical Name | 1-[2-(1-{4-[(4-aminocarbamoylpiperidin-1-yl)methyl]phenyl}-N-methylformamido)ethyl]piperidin-4-yl N-{[1,1'-biphenyl]-2-yl}carbamate

Molecular Formula | C₃₅H₄₃N₅O₄

Molecular Weight | 601.75

Target | Muscarinic receptors (M₁-M₅, with higher kinetic selectivity for M₃ receptors, dissociation t₁/₂ = 82 minutes vs 6.9 minutes for M₂) NCBI

Developer | Theravance Biopharma (original developer), co-developed with Mylan (now Viatris)

Market Launch Date | November 2018 (US FDA); Not yet approved in China

Dosage Form and Strength | Nebulizer solution: 175 μg/3mL/vial (single-dose vial) NCBI

II. Physicochemical Properties

Parameter | Data

Appearance | White to off-white powder

Solubility | Easily soluble in water (approximately 10 mg/mL, 25℃), slightly soluble in ethanol, sparingly soluble in n-hexane

Dissociation Constant (pKa) | 9.2 (piperidine ring), 7.8 (amide group) (predicted value)

Stability | Stable for 24 months at 25℃/60% RH, stored in a sealed, cool, and dry place; Nebulizer solution is stable for 24 hours at 25℃ after preparation, do not freeze.

Chiral Characteristics | Contains 3 chiral centers, a single configurational isomer, optical purity >99.5%

Partition Coefficient (logP) | 4.5 (predicted value)

III. Mechanism of Action (Core Advantage)

M₃ receptor kinetic selectivity: Slow dissociation from airway smooth muscle M₃ receptors (t₁/₂ = 82 minutes), M₂ receptor dissociation is rapid (t₁/₂ = 6.9 minutes), providing sustained bronchodilation and reducing acetylcholine-mediated airway constriction (NCBI).

Lung-targeted metabolic design: The terminal amide bond is stable in lung tissue, but rapidly hydrolyzed into inactive metabolites after entering the bloodstream, resulting in extremely low systemic exposure (oral bioavailability is only 3%). The incidence of anticholinergic side effects such as dry mouth and constipation is significantly lower than that of tiotropium (NCBI).

Once-daily long-acting maintenance: The bronchodilatory effect after nebulization lasts for 24 hours, significantly improving FEV₁ and reducing the risk of COPD exacerbations by 15%-18%.

Strong nebulization compatibility: No inspiratory coordination is required, making it suitable for elderly patients, those with cognitive impairment, or those with insufficient inspiratory flow, thus improving medication adherence (PMC).