N,N-双乙酰胱氨酸在毕格犬体内的药动学

Pharmacokinetics of N,N-diacetylcystine in Beagle dogs

目的研究毕格犬静脉注射不同剂量N，N-双乙酰胱氨酸（DiNAC）后的药动学。方法毕格犬12只随机分成3组，分别静脉注射DiNAC25，12．5，6．25mg／kg，在设定的时间点采血，反相高效液相色谱法测定血浆中的DiNAC浓度，DAS程序计算其药动学参数。结果毕格犬静脉给予DiNAC后，其血药浓度-时间曲线符合二室模型一级动力学过程。AUC0→∞分别为3849．7±157．7，1683．0±90．5，757．1±344．2mg／（L·min），与给药剂量成良好的线性关系（r=0．9993）；Cmax分别为91．99±15．13，53．37±3．88，23．20±7．07mg／L，与给药剂量呈线性关系（r=0．993）；而t1／2α为1、1～1．9min，t1／2β为34．2～47．3min，分布容积（Vd）为0、38～0．49L／kg，显示非剂量依赖性特征。结论DiNAC在毕格犬体内的药动学过程为二室模型一级动力学过程，具有分布快，消除迅速的特点。

Purpose To study the iv pharmacokinetics of N, N-diacetylcystine （DiNAC）in Beagle dogs. Methods 12 Beagle dogs were divided into 3 groups.A single dose of 25, 12.5 and 6.25 mg/kg of DiNAC was given by iv. Serial blood samples were collected at the designed time points. The plasma DiNAC concentration was measured by RP-HPLC. Pharmacokinetic parameters were computerized by DAS program. Results After intravenous injection of single dose DiNAC, the plasma concentration versus time curves of DiNAC conformed to two-compartment model. The AUC0→∞ and Cmax were lined with the iv dose （ r = 0. 999 3 and 0.993, respectively） ; t1/2α was 1.1-1.9 min, t1/2β was 34.2-47.3 min and Vd was 0.38-0.49 L/kg, which had no significant deviation between groups （ P 〉 0.05 ）. Condusion The pharmacokinetics of DiNAC con- formed to two-compartment model in Beagle dogs after single dose iv. Distribution and elimination of DiNAC were rapid.