Gomita Y, Yamori M, Furuno K, Araki Y
Department of Hospital Pharmacy, Okayama University Medical School, Japan.
Pharmacology. 1989;38(6):388-96. doi: 10.1159/000138562.
Influences of emotional stress on nicorandil pharmacokinetics were studied in rats that received physical and psychological stimuli (referred to as 'sender' and 'responder' rats, respectively) using the communication box paradigm. Concerning pharmacokinetic, there was no marked difference in the Tmax, Ka, Kel, T1/2 and Vd between the sender rats and the nonstressed control rats when both of which were orally administered 10 mg/kg of nicorandil. But the Cmax and AUC were lower and clearance (Cl) was higher in the sender rats. In the responder rats, there was no difference in Tmax, Ka, Kel, and T1/2. But the Cmax and AUC were lower and the Vd was higher than those of the control rats. On the other hand, when nicorandil was administered in a dose of 5 mg/kg subcutaneously, Tmax and T1/2 in the sender rats did not differ from those of the controls, but the Cmax, Ka and AUC were lower, and the Kel, Vd and Cl were higher. Between the responder and control rats, significant differences were found in all parameters except for Vd, i.e., Cmax, Ka, T1/2 and AUC were lower than those of control rats, and the Tmax, Kel and Cl were higher than those of control rats. This indicates that pharmacokinetics of nicorandil when administered orally and subcutaneously were influenced not only by physical stress but also by psychological stress.
采用通讯箱范式，在接受身体和心理刺激的大鼠（分别称为“发送者”和“应答者”大鼠）中研究了情绪应激对尼可地尔药代动力学的影响。关于药代动力学，当口服给予10mg/kg尼可地尔，“发送者”大鼠与无应激对照组大鼠之间的达峰时间（Tmax）、吸收速率常数（Ka）、消除速率常数（Kel）、半衰期（T1/2）和分布容积（Vd）没有显著差异。但“发送者”大鼠的血药浓度峰值（Cmax）和药时曲线下面积（AUC）较低，清除率（Cl）较高。在“应答者”大鼠中，Tmax、Ka、Kel和T1/2没有差异。但Cmax和AUC低于对照组大鼠，Vd高于对照组大鼠。另一方面，当皮下注射5mg/kg剂量的尼可地尔时，“发送者”大鼠的Tmax和T1/2与对照组无差异，但Cmax、Ka和AUC较低，Kel、Vd和Cl较高。在“应答者”大鼠与对照组大鼠之间，除Vd外的所有参数均存在显著差异，即Cmax、Ka、T1/2和AUC低于对照组大鼠，Tmax、Kel和Cl高于对照组大鼠。这表明口服和皮下注射尼可地尔时的药代动力学不仅受到身体应激的影响，还受到心理应激的影响。
