Predicting muscarinic receptor occupancy in human bladder mucosa from urinary concentrations of antimuscarinic agents for overactive bladder.
Drug Metab Pharmacokinet
; 56: 100998, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38583388
ABSTRACT
To assess the pharmacologically relevant and selective muscarinic receptor occupancy in the bladder mucosa, we considered not only plasma drug concentrations but also urinary drug concentrations. The purpose of this study was to predict muscarinic receptor occupancy in the human bladder mucosa based on urinary concentrations in response to clinical dosages of antimuscarinic agents used to treat overactive bladder. The calculated mean plasma or serum unbound steady state concentrations were 0.06-11 nM in clinical dosages of five antimuscarinic agents. Urinary concentrations calculated from the mean plasma or serum and renal clearance ranged between 19 nM and 2 µM, which were >10-fold higher than the Ki values for bladder muscarinic receptors excluding propiverine. Bladder mucosal muscarinic receptor occupancy estimated from the urinary concentrations and the Ki values was >90 % at a steady state in clinical dosages of five antimuscarinic agents. The bladder muscarinic receptor occupancy was higher than that in the parotid gland calculated based on the mean plasma or serum unbound concentrations and Ki values for muscarinic receptors in the parotid gland. These results suggest that sufficient and selective muscarinic receptor occupancy by antimuscarinic agents, to exert pharmacological effects, in the bladder mucosa can be predicted using urinary concentrations.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Vejiga Urinaria
/
Receptores Muscarínicos
/
Antagonistas Muscarínicos
/
Vejiga Urinaria Hiperactiva
/
Membrana Mucosa
Límite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Drug Metab Pharmacokinet
/
Drug metab. pharmacokineti
/
Drug metabolism and pharmacokinetics
Asunto de la revista:
FARMACOLOGIA
/
METABOLISMO
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón