Biotransformation and disposition characteristics of HSK7653, a novel long-acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes.
Diabetes Obes Metab
; 26(7): 2860-2868, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38646838
ABSTRACT
AIM:
To investigate the metabolism and disposition characteristics of HSK7653 in healthy male Chinese participants.METHODS:
A single oral dose of 80 µCi (25 mg) [14C]HSK7653 capsules was administered to six healthy participants, and blood, plasma, urine and faeces were collected. Quantitative and qualitative analysis was conducted to investigate the pharmacokinetics, blood-to-plasma ratio, mass balance and metabolism of HSK7653.RESULTS:
The drug was well absorbed and reached a maximum concentration at 1.25 h. The drug-related components (HSK7653 and its metabolites) were eliminated slowly, with a half-life (t1/2) of 111 h. Unchanged HSK7653 contributed to more than 97% of the total radioactivity in all plasma samples. The blood-to-plasma ratio (0.573-0.845) indicated that HSK7653 did not tend to distribute into blood cells. At 504 h postdose, up to 95.9% of the dose was excreted, including 79.8% in urine and 16.1% in faeces. Most of the radioactivity (75.5% dose) in excreta was unchanged HSK7653. In addition, nine metabolites were detected in urine and faeces. The most abundant metabolite was M6-2, a dioxidation product of HSK7653, which accounted for 4.73% and 2.63% of the dose in urine and faeces, respectively. The main metabolic pathways of HSK7653 in vivo included oxidation, pyrrole ring opening and sulphonamide hydrolysation.CONCLUSION:
HSK7653 was well absorbed, slightly metabolized and slowly excreted in humans. The high plasma exposure and long t1/2 of HSK7653 may contribute to its long-lasting efficacy as a long-acting dipeptidyl peptidase-4 inhibitor.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Tipo 2
/
Inhibidores de la Dipeptidil-Peptidasa IV
Límite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
Diabetes Obes Metab
Asunto de la revista:
ENDOCRINOLOGIA
/
METABOLISMO
Año:
2024
Tipo del documento:
Article
País de afiliación:
China