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盐酸卡替洛尔口腔崩解片在Beagle犬体内的药动学研究
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| 篇名： | 盐酸卡替洛尔口腔崩解片在Beagle犬体内的药动学研究 |
| TITLE： | |
| 摘要： | 目的：建立测定Beagle犬血浆中盐酸卡替洛尔质量浓度的方法，并对盐酸卡替洛尔口腔崩解片在Beagle犬体内的药动学行为进行研究。方法：采用乙腈沉淀法预处理血浆样品。采用高效液相色谱法（HPLC）测定血药浓度，色谱柱为VP-ODS C18，流动相为乙腈-0.067％磷酸氢二钠溶液（13 ∶ 87，V/V），检测波长为251 nm，柱温为30 ℃，流速为1.0 mL/min，进样量为20 μL。取健康Beagle犬6只，采用双制剂双周期自身交叉给药方式，分别给予自制盐酸卡替洛尔口腔崩解片（受试制剂）和进口盐酸卡替洛尔片（参比制剂），剂量均为15 mg/只；于相应时间点取静脉血，测定血浆中盐酸卡替洛尔的血药浓度。采用DAS 2.0软件分别计算两种制剂的药动学参数，并计算受试制剂的相对生物利用度（F）；采用SPSS 20.0软件比较两种制剂的药动学参数差异。结果：盐酸卡替洛尔血药浓度在9.77～1 250 ng/mL（r＝0.999 7）范围内线性关系良好，定量限和检测限分别为3.6、1.2 ng/mL；提取回收率大于80％；精密度、稳定性试验RSD均小于12％，准确度相对误差均值在－8％～－2％以内。盐酸卡替洛尔口腔崩解片在Beagle犬体内的主要药动学参数cmax为（327.82±17.27）ng/mL，tmax为（0.54±0.10）h，AUC0-24 h为（1 136.09±172.69）ng·h/mL，AUC0-∞为（1 243.52±190.08）ng·h/mL；与参比制剂比较，F0-24 h为93.03％，F0-∞为95.45％。两种制剂的lncmax和tmax差异均有统计学意义（P＜0.05），lnAUC0-24 h差异无统计学意义（P＞0.05）。结论：建立的HPLC法简单、快速、准确，精密度和灵敏度较高，可用于盐酸卡替洛尔口腔崩解片在Beagle犬体内的药动学研究；与进口普通片比较，盐酸卡替洛尔口腔崩解片在Beagle犬体内的吸收速度更快，而吸收程度无显著性差异。 |
| ABSTRACT： | OBJECTIVE： To establish the method for the determination of carteolol hydrochloride concentration in plasma of Beagle dogs， and to study pharmacokinetics of Carteolol hydrochloride orally disintegrating tablets in Beagle dogs. METHODS： The plasma samples were pre-treated by acetonitrile precipitation. HPLC method was adopted. The determination was performed on VP-ODS C18 column with mobile phase consisted of acetonitrile-0.067％ disodium hydrogen phosphate solution （13 ∶ 87，V/V） at flow rate of 1.0 mL/min； the detection wavelength was set at 251 nm； the column temperature was 30 ℃； the sample size was 20 μL. Six healthy Beagle dogs were selected and given self-prepared Carteolol hydrochloride orally disintegrating tablets （test preparation） or imported Carteolol hydrochloride tablets （reference preparation）， 15 mg/dog by the way of double-preparation double-cycle crossover administration. Venous blood samples were collected at corresponding time points， and plasma concentration of carteolol hydrochloride was determined. The pharmacokinetic parameters of two preparations were calculated by using DAS 2.0 software， and relative bioavailability （F） of test preparation was calculated. The pharmacokinetic parameters of two preparations were compared by SPSS 20.0 software. RESULTS： The linear range of carteolol hydrochloride concentration in plasma was 9.77-1 250 ng/mL （r＝0.999 7）. The limits of quantitation and detection were 3.6 and 1.2 ng/mL， respectively. The extraction recovery rates were higher than 80％； RSDs of precision and stability tests were all lower than 12％； average RE of accuracy were within －8％ to －2％. The main pharmacokinetic parameters of Carteolol hydrochloride orally disintegrating tablets in Beagle dogs were as follows as cmax of （327.82±17.27） ng/mL， tmax of （0.54±0.10） h， AUC0-24 h of （1 136.09±172.69） ng·h/mL， AUC0-∞ of （1 243.52±190.08） ng·h/mL； compared with reference preparation， F0-24 h was 93.03％， F0-∞ was 95.45％. There was statistical significance in lncmax and tmax （P＜0.05）， but no statistical significance in lnAUC0-24 h （P＞0.05） between 2 kinds of preparations. CONCLUSIONS： The established HPLC method is simple， rapid， accurate， precise and sensitive， and can be used for pharmacokinetic study of Carteolol hydrochloride orally disintegrating tablets in Beagle dogs. Compared with imported tablet， absorption rate of Carteolol hydrochloride orally disintegrating tablets in Beagle dogs is faster， without significant difference in absorption degree. |
| 期刊： | 2018年第29卷第18期 |
| 作者： | 罗玲艳，张平，张贺，聂延君，罗永煌，罗雷 |
| AUTHORS： | LUO Lingyan，ZHANG Ping，ZHANG He，NIE Yanjun，LUO Yonghuang，LUO Lei |
| 关键字： | 盐酸卡替洛尔；口腔崩解片；高效液相色谱法；Beagle犬；药动学；生物利用度 |
| KEYWORDS： | Carteolol hydrochloride； Orally disintegrating tablets； HPLC； Beagle dogs； Pharmacokinetics； Bioavailability |
| 阅读数： | 270 次 |
| 本月下载数： | 4 次 |
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