Scasnár V, Kállay Z, Bezek S, Trnovec T, Durisovă M
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
Arzneimittelforschung. 1987 Jul;37(7):783-7.
Pharmacokinetics of a local anaesthetic of the carbanilate type (Heptacaine; in the following briefly called HCP), was studied using a labelled product, N-[2-(2-[1-14C]-heptyloxyphenylcarbamoyloxy)ethyl]piperidinum++ + chloride. Determination of HCP in biological material was based on double extraction of HCP from alkaline media into n-heptane. The plasma concentration of HCP following i.v. administration to rats was approximated by a biexponential function. An open two-compartment pharmacokinetic model was conferred to the data. The model parameter estimates are as follows: terminal elimination half-life 3.80 +/- 0.15 h, distribution volume at steady state 9.31 l/kg, total body clearance 73.4 ml/min/kg, mean residence time 2.1 h. The systemic availability of the orally given HCP in solution was 35.8%. The HCP plasma AUC vs. dose relationship was linear within doses ranging from 2.78 to 4.33 mg/kg. The brain uptake index of HCP in comparison with 3H2O was 62.2%. Autoradiography in mice injected i.v. showed a heterogeneous distribution of the label in the tissues and its excretion by the urinary and biliary pathways. HCP showed strong affinity to the lung tissue. During 96 h after i.v. administration, 21% and 62% of the 14C dose was excreted into urine and faeces, respectively, and after oral administration, the excretion was 17% and 43%, respectively.
使用标记产物N-[2-(2-[1-¹⁴C]-庚氧基苯基氨基甲酰氧基)乙基]哌啶鎓氯化物，研究了氨基甲酸酯类局部麻醉剂（庚卡因；以下简称HCP）的药代动力学。生物材料中HCP的测定基于将HCP从碱性介质中双重萃取到正庚烷中。静脉注射给大鼠后HCP的血浆浓度用双指数函数近似。对数据赋予了一个开放的二室药代动力学模型。模型参数估计如下：终末消除半衰期3.80±0.15小时，稳态分布容积9.31升/千克，全身清除率73.4毫升/分钟/千克，平均驻留时间2.1小时。口服溶液中HCP的全身可用性为35.8%。在2.78至4.33毫克/千克的剂量范围内，HCP血浆AUC与剂量的关系呈线性。与³H₂O相比，HCP的脑摄取指数为62.2%。静脉注射的小鼠的放射自显影显示标记物在组织中的分布不均匀，并且通过尿液和胆汁途径排泄。HCP对肺组织表现出很强的亲和力。静脉注射后96小时内，¹⁴C剂量的21%和62%分别排泄到尿液和粪便中，口服给药后，排泄率分别为17%和43%。
