Effect of age on the pharmacokinetics of polymorphic nimodipine in rats after oral administration

Acta Pharmaceutica Sinica B

Mingshi Yang¹  Dianshu Yin²  Yongli Wang³  Zhenping Wei³  Junbo Gong³  Ruilian Chen³  Yi Li³  Kaixuan Zhang³  Wenli Liu³  Xiaona Wang³  Yao Li³  Duanyun Si⁴ 

[1] Faculty of Pharmaceutical Science, University of Copenhagen, Copenhagen, Denmark;Pharmaceutical Research Institute, Shijiazhuang No. 4 Pharmaceutical Company, Shijiazhuang 052165, China;School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China;State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China;

关键词: Nimodipine;    Age difference;    Polymorphic drug;    Pharmacokinetics;    Crystal form;   

DOI  :  10.1016/j.apsb.2016.07.010

来源: DOAJ

【 摘 要 】

The previous investigation has proved that their existed pharmacokinetic difference between the different crystal forms of the polymorphic drugs after oral administration. However, no systemic investigations have been made on the change of this pharmacokinetic difference, resulted either from the physiological or from the pathological factors. In this paper, we used polymorphic nimodipine (Nim) as a model drug and investigated the effect of age difference (2- and 9-month old) on the pharmacokinetics after oral delivery in rats. As the results shown, for L-form of Nim (L-Nim), the AUC0–24 h in 2-month-old rats was 343.68±47.15 ng·h/mL, which is 23.36% higher than that in 9-month-old rats. For H-form of Nim (H-Nim), the AUC0–24 h in 2-month-old rats was 140.91±19.47 ng·h/mL, which is 54.64% higher than that in 9-month-old rats. The AUC0–24 h ratio between H-Nim and L-Nim was 2.44 in 2-month-old rats and 3.06 in 9-month-old rats. Since age difference could result in unparallelled change of the absorption and bioavailability of the polymorphic drugs, the results in this experiment are of value for further investigation of crystal form selection in clinical trials and rational clinical application of the polymorphic drugs.

【 授权许可】

Unknown