The Impact of Dextran Sodium Sulfate-Induced Gastrointestinal Injury on the Pharmacokinetic Parameters of Donepezil and Its Active Metabolite 6-O-desmethyldonepezil, and Gastric Myoelectric Activity in Experimental Pigs.
Molecules
; 26(8)2021 Apr 09.
Article
en En
| MEDLINE
| ID: mdl-33918638
ABSTRACT
Gastrointestinal side effects of donepezil, including dyspepsia, nausea, vomiting or diarrhea, occur in 20-30% of patients. The pathogenesis of these dysmotility associated disorders has not been fully clarified yet. Pharmacokinetic parameters of donepezil and its active metabolite 6-O-desmethyldonepezil were investigated in experimental pigs with and without small intestinal injury induced by dextran sodium sulfate (DSS). Morphological features of this injury were evaluated by a video capsule endoscopy. The effect of a single and repeated doses of donepezil on gastric myoelectric activity was assessed. Both DSS-induced small intestinal injury and prolonged small intestinal transit time caused higher plasma concentrations of donepezil in experimental pigs. This has an important implication for clinical practice in humans, with a need to reduce doses of the drug if an underlying gastrointestinal disease is present. Donepezil had an undesirable impact on porcine myoelectric activity. This effect was further aggravated by DSS-induced small intestinal injury. These findings can explain donepezil-associated dyspepsia in humans.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Piperidinas
/
Estómago
/
Complejo Mioeléctrico Migratorio
/
Tracto Gastrointestinal
/
Metaboloma
/
Donepezilo
/
Indanos
Límite:
Animals
Idioma:
En
Revista:
Molecules
Asunto de la revista:
BIOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
República Checa