Absorption and efflux characteristics of CP-25 in plasma and peripheral blood mononuclear cells of rats by UPLC-MS/MS.
Biomed Pharmacother
; 108: 1651-1657, 2018 Dec.
Article
em En
| MEDLINE
| ID: mdl-30372867
ABSTRACT
Paeoniflorin-6'-O-benzene sulfonate (code CP-25), is an active monomer obtained by modifying the structure of paeoniflorin (Pae). CP-25 can alleviate the course of adjuvant arthritis (AA) rats by regulating immune inflammatory response and reducing bone damage. In addition, our research has found that immune cells are important target cells for its anti-inflammatory and immunomodulatory effects. Therefore, it is of great significance to study the pharmacokinetics of CP-25 in immune cells. The aim of this study was to investigate the absorption and efflux of CP-25 in plasma and peripheral blood mononuclear cells (PBMCs) of rats. We established a sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to rapidly determine CP-25 in plasma and PBMC of rat. We found that the transport amount of CP-25 in PBMC gradually decreased with the increase of time, and reached equilibrium after 1 h. Moreover, there is a certain correlation between the concentration of CP-25 in plasma and the concentration of CP-25 in PBMC. In addition, we used several transporter inhibitors to study their effects on the efflux of CP-25 in PBMC. The efflux of CP-25 in PBMC increased with the increase of time in the first 30 min, and the efflux of CP-25 decreased gradually after 30 min. Furthermore, after multiple administration of 50 mg/kg in rats, concentration of CP-25 in PBMC is similar to the change of concentration of CP-25 in plasma. Our results suggest that CP-25 may enter PBMC by passive transport, and P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) may be involved in the efflux of CP-25 in PBMC. This research provides a basis and guidance for further study of the clinical application of CP-25.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucócitos Mononucleares
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Monoterpenos
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Espectrometria de Massas em Tandem
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Absorção Fisiológica
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Glucosídeos
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Biomed Pharmacother
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China