Pharmacokinetics of two kinds of nimodipine crystal tablets in rhesus monkey
10.16438/j.0513-4870.2017-0638
- VernacularTitle:两种晶型尼莫地平片剂在恒河猴体内药代动力学研究
- Author:
Qi-meng ZHOU
1
;
Jun-ke SONG
1
;
Cheng XING
2
;
Jin-hua WANG
1
;
Yang LÜ
2
;
Guan-hua DU
1
Author Information
1. Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
2. Research Centre of Polymorphic Drugs, Beijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
nimodipine;
powder X-ray diffraction;
rhesus;
pharmacokinetics;
LC-MS
- From:
Acta Pharmaceutica Sinica
2017;52(12):1918-1923
- CountryChina
- Language:Chinese
-
Abstract:
Nimodipine is a selective calcium channel antagonist of cerebral vessels smooth muscle and also has polymorphs. It hasn't been reported that different crystal forms influence the metabolism process in huge animals like rhesus monkeys in vivo. This article may provide reference in the control of the quality of nimodipine and quality consistency evaluation. The powder X-ray diffraction (PXRD) method was used to identify different crystal forms and the dissolution test in vitro was used to detect the dissolution. The LC-MS method of assay nimodipine in rhesus monkey plasm was established to determine pharmacokinetics characters of different tablets from different crystal forms in rhesus monkey in vivo. As a result, the tablets inherit difference crystal forms and the dissolution of reference tablets is 1.3% higher than crystal tablets. However, the maximal blood concentration (Cmax) of crystal tablet was 37.3% higher than reference tablet and AUC of crystal tablet was 29.8% higher than reference tablet. After administrated 2.5 mg·kg-1 orally, calculated pharmacokinetics characters were observed as following:Cmax was 381.4 ±327.3 and 178.0 ±214.8 μg·L-1; AUC0-t was 853.1 ±500.7 and 646.5 ±430.3 μg·L-1·h respectively. The serum concentration result of different nimodipine tablets in rhesus monkeys in vivo suggests that polymorphs has a significantly distinction, which points out that controlling the crystal forms of nimodipine is essential to ensure the therapeutic efficacy. It is essential to execute quality consistency evaluation.
