Comparison of pharmacokinetics and bioavailability of prednisone acetate and prednisone in Beagle dogs
10.16438/j.0513-4870.2019-1053
- VernacularTitle:醋酸泼尼松和泼尼松在Beagle犬体内的生物利用度比较
- Author:
Cai-feng WU
1
;
Yun-ting ZHU
2
;
Yi-fan ZHANG
2
;
Da-fang ZHONG
1
Author Information
1. College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Publication Type:Research Article
- Keywords:
LC-MS/MS;
prednisone acetate;
prednisone;
prednisolone;
bioavailability
- From:
Acta Pharmaceutica Sinica
2020;55(6):1251-1256
- CountryChina
- Language:Chinese
-
Abstract:
An LC-MS/MS method was developed for the simultaneous determination prednisone acetate, prednisone and active metabolite prednisolone in dog plasma, and applied to a bioavailability and pharmacokinetics study of oral dose of prednisone acetate (2.0 mg·kg-1) and prednisone (1.8 mg·kg-1) given to Beagle dogs in a randomized, two-way crossover study. This experiment scheme was approved by the Experimental Animal Ethics Committee of Shanghai Institute of Medicine, Chinese Academy of Sciences. Dexamethason was used as internal standard. After extraction from the plasma by protein precipitation, the analytes and internal standard were separated on an HSS T3 (50 mm×2.1 mm, 1.8 μm) column using a gradient elution procedure. The mobile phase consisted of methanol and 5 mmol·L-1 ammonium acetate aqueous solution (0.1% formic acid). Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 401.2→295.2 for prednisone acetate, m/z 359.2→313.2 for prednisone, m/z 361.2→325.1 for prednisolone, m/z 393.2→373.0 for dexamethason. After prednisone acetate was administered, the Cmax of prednisone was (25.1 ± 3.61) ng·mL-1 and AUC0-t was (115 ± 27.2) h·ng·mL-1, while the Cmax of prednisolone was (207 ± 38.5) ng·mL-1 and AUC0-t was (760 ± 218) h·ng·mL-1. After prednisone was administered, the Cmax of prednisone was (67.9 ± 22.6) ng·mL-1 and AUC0-t was (160 ± 19.3) h·ng·mL-1, while the Cmax of prednisolone was (582 ± 81.4) ng·mL-1 and AUC0-t was (1 310 ± 140) h·ng·mL-1. The relative bioavailability of prednisone acetate to prednisone was only 57.1%.
