A Preliminary Study of Pharmacokinetics and Pharmacodynamics of Oral Fingolimod in Dogs.
In Vivo
; 37(5): 2128-2133, 2023.
Article
em En
| MEDLINE
| ID: mdl-37652477
ABSTRACT
BACKGROUND/AIM:
Fingolimod is a sphingosine-1-phosphate receptor modulator that prevents lymphocytes egress from lymphoid organs. It has been used as a disease-modifying drug for human multiple sclerosis and has shown better therapeutic effects than other conventional therapies. Therefore, this study was performed to obtain preclinical data of fingolimod in dogs. MATERIALS ANDMETHODS:
Nine laboratory Beagle dogs were used and randomized into three groups for pharmacokinetics (PK) and pharmacodynamics (PD). The dogs were administered once with a low-dose (0.01 mg/kg, n=3), medium-dose (0.05 mg/kg, n=3), and high-dose (0.1 mg/kg, n=3) of fingolimod, orally. Samples were collected serially at predetermined time points, and whole blood fingolimod concentrations were measured using high-performance liquid chromatography-mass spectrometry. Differential counts of leukocytes over time were determined to identify immune cells' response to fingolimod.RESULTS:
Regarding PK, the concentration of fingolimod in the blood increased in a dose-dependent manner, but it was not proportional. Regarding PD, the number of lymphocytes significantly decreased compared to baseline in all dose groups (low-dose, p=0.0002; medium-dose, p<0.0001; high-dose, p=0.0012). Eosinophils were significantly reduced in low- (p=0.0006) and medium- (p=0.0006) doses, and neutrophils were also significantly reduced in medium-(p=0.0345) and high- (p=0.0016) doses.CONCLUSION:
This study provides the basis for future clinical applications of fingolimod in dogs with immune-mediated diseases, such as meningoencephalitis of unknown etiology.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cloridrato de Fingolimode
Tipo de estudo:
Clinical_trials
Limite:
Animals
Idioma:
En
Revista:
In Vivo
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2023
Tipo de documento:
Article