Pharmacokinetics of levornidazole disodium phosphate in monkey
10.16438/j.0513-4870.2017-0996
- VernacularTitle:磷酸左奥硝唑酯二钠在食蟹猴体内的药代动力学研究
- Author:
Qian ZHAO
1
;
Li-li LI
1
;
Pei HU
1
;
Wen ZHONG
1
;
Fei DING
2
;
Shu-tian JIA
2
;
Zheng-fang HU
2
;
Wen-bo LIU
2
;
Ji JIANG
1
Author Information
1. Clinical Pharmacology Research Centre & Translational Medicine Centre, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
2. Yangtze River Pharmaceutical Group Nanjing Hailing Pharmaceutical Co., Ltd, Nanjing 210000, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
levornidazole disodium phosphate;
levornidazole;
stable isotope labeled drug;
bioequiva-lence;
pharmacokinetics
- From:
Acta Pharmaceutica Sinica
2018;53(1):90-96
- CountryChina
- Language:Chinese
-
Abstract:
This study was carried out to investigate the pharmacokinetics/bioequivalence of levornidazole disodium phosphate by using stable isotope labeled drug, evaluated the pharmacokinetic profile and confirmed the prodrug characteristics of levornidazole disodium phosphate in monkey. Levornidazole (Drug A) and stable isotope 15N labeled levornidazole disodium phosphate (Drug B) were mixed with equal mole amount (experiment I); stable isotope 15N labeled levornidazole disodium phosphate (Drug B) and levornidazole disodium phosphate (Drug C) were mixed with equal mole amount, respectively. After giving the mixed drugs to the monkey, the concentration of 15N-levornidazole disodium phosphate, levornidazole disodium phosphate, 15N-levornidazole and levornidazole in plasma samples of pre-dosing and 24 h after administration were analyzed by a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method. Pharmacokinetic calculations were performed through non-compartmental analysis using WinNonlin software. Two-sided 90% confidence intervals (CI) were used to evaluate the bioequivalence of two drugs. The results showed that levornidazole disodium phosphate was metabolized to levornidazole rapidly after administration, the body exposure were increased with the dosage. The method of bioequivalence used in this study was different from the traditional two periods, crossover design. By using the method of this study, the effects of administration period, intra-individual variability, and sequence of administration on bioequivalence were avoided. The results of this study had successfully supported the pharmacokinetic and bioequivalence study of this drug in human using the same approach.
