间硝苯地平在Beagle犬体内的药代动力学

Pharmacokinetics of m-nifedipine in Beagle dogs

目的 用反相高效液相色谱法研究间硝苯地平 (m nifedipine ,m Nif)在Beagle犬体内的药代动力学特征。方法 正交设计优化色谱分离条件 ,Beagle犬分别iv给予m Nif 0 2 88mg·kg- 1 和igm Nif 1 15 2 ,3 4 5 6 ,10 370mg·kg- 1 。用反相高效液相色谱法分析血浆中原型药物浓度 ,血浆药物浓度 时间数据用 3P97药代动力学软件分析。结果 Beagle犬ivm Nif,其体内过程符合二室模型 ,T1 2 β为 116 8min ;ig给予m Nif后在Beagle犬体内的代谢符合一室模型 ,其中低剂量 (1 15 2mg·kg- 1 )组Cmax为 2 0 μg·L- 1 ,T1 2 (Ke)为 14 7min ;中剂量 (3 4 5 6mg·kg- 1 )组Cmax为 36μg·L- 1 ,T1 2 (Ke)为 12 2min ;高剂量 (10 37mg·kg- 1 )组Cmax为 6 9μg·L- 1 ,T1 2 (Ke)为 14 4min。结论 Beagle犬ig和ivm Nif后 ,血浆中药物消除迅速 。

Aim To study the pharmacokinetics of m-nifedipine (m-Nif) in Beagle dogs. Methods The Beagle dogs were divided into two groups. m-Nif was intravenously administered to the Beagle dogs in group 1 at the dose of 0.288 mg·kg -1, and it was orally administered to the Beagle dogs in group 2,3 and 4 at the dose of 1.152, 3.456 and 10.370 mg·kg -1, respectively. m-Nif in plasma was detected by reversed phase high performance liquid chromatography. The pharmacokinetic parameters were calculated by 3P97 software. Results When m-Nif was intravenously administered, the plasma concentration-time curve was fit to a two-compartment model and T 1/2β was 117 min. When m-Nif was orally administered, the plasma concentration-time curve was fit to a one-compartment model. T 1/2(K e) and C max were 147 min and 20 μg·L -1; at the low dose of 1.152 mg·kg -1. T 1/2(K e) was 122 min and C max was 36 μg·L -1 at the middle dose of 3.456 mg·kg -1. T 1/2(K e)was 144 min and C max was 69 μg·L -1 at the high dose of 10.37 mg·kg -1, respectively. Conclusion It was showed that the speed of elimination of m-Nif was high in Beagle dogs. The absolute bioavailability of m-Nif given orally was very low.