采用不同的离体方法在弗兰兹扩散池（Franz cells）中测定拉米夫定和齐多夫定的渗透性。
Determination of lamivudine and zidovudine permeability using a different ex vivo method in Franz cells.
作者信息
Dezani André Bersani, Pereira Thaisa Marinho, Caffaro Arthur Massabki, Reis Juliana Mazza, Serra Cristina Helena Dos Reis
机构信息
Faculty of Pharmaceutical Sciences of the University of São Paulo, Avenida Professor Lineu Prestes, 580, Bl. 13, 05508-000, São Paulo, SP, Brazil.
出版信息
J Pharmacol Toxicol Methods. 2013 May-Jun;67(3):194-202. doi: 10.1016/j.vascn.2013.01.005. Epub 2013 Jan 19.
INTRODUCTION
The major processes that control the absorption of orally administered drugs are dissolution and gastrointestinal permeation. These processes depend on two main properties: solubility and permeability. Based on these characteristics, the Biopharmaceutical Classification System (BCS) was proposed as a tool to assist in biowaiver and bioavailability prediction of drugs.
METHODS
The purpose of the present study was to evaluate the permeability of lamivudine (3TC) and zidovudine (AZT) using a different ex vivo method in Franz cells. A segment of jejunum was inserted in a Franz cells apparatus, in order to assess drug permeability in the apical-basolateral (A-B) and basolateral-apical (B-A) directions. Each drug was added to the donor chamber, collected from the acceptor chamber and analyzed by HPLC. Fluorescein (FLU) and metoprolol (METO) were used as low and high permeability markers, respectively.
RESULTS
The apparent permeability (Papp) results for the A-B direction were: Papp FLU A-B=0.54×10(-4)cm·s(-1), Papp METO A-B=7.99×10(-4)cm·s(-1), Papp 3TC A-B=4.58×10(-4)cm·s(-1) and Papp AZT A-B=5.34×10(-4)cm·s(-1). For the B-A direction, the Papp results were: Papp FLU B-A=0.56×10(-4)cm·s(-1), Papp METO B-A=0.25×10(-4)cm·s(-1), Papp 3TC B-A=0.24×10(-4)cm·s(-1) and Papp AZT B-A=0.19×10(-4)cm·s(-1).
DISCUSSION
For the A-B direction, the Papp results of fluorescein and metoprolol show low and high permeability, respectively, indicating that the membranes were appropriate for permeability studies. For the A-B direction, the Papp results of 3TC and AZT suggest that these antiretroviral drugs have permeability values close to metoprolol. Nevertheless, for the B-A direction the Papp results do not suggest efflux mechanism for any of the drugs. Thereby, the different ex vivo methods using Franz cells can be successfully applied in drug permeability studies, in particular for drug biopharmaceutical classification.
引言
控制口服药物吸收的主要过程是溶解和胃肠道渗透。这些过程取决于两个主要特性：溶解度和渗透性。基于这些特性，提出了生物药剂学分类系统（BCS）作为辅助药物生物豁免和生物利用度预测的工具。
方法
本研究的目的是使用Franz扩散池中的不同离体方法评估拉米夫定（3TC）和齐多夫定（AZT）的渗透性。将一段空肠插入Franz扩散池装置中，以评估药物在顶端-基底（A-B）和基底-顶端（B-A）方向的渗透性。将每种药物添加到供体池中，并从受体池中收集，然后通过高效液相色谱法进行分析。分别使用荧光素（FLU）和美托洛尔（METO）作为低渗透性和高渗透性标记物。
结果
A-B方向的表观渗透率（Papp）结果为：Papp FLU A-B = 0.54×10⁻⁴cm·s⁻¹，Papp METO A-B = 7.99×10⁻⁴cm·s⁻¹，Papp 3TC A-B = 4.5 8×10⁻⁴cm·s⁻¹，Papp AZT A-B = 5.34×10⁻⁴cm·s⁻¹。对于B-A方向，Papp结果为：Papp FLU B-A = 0.56×10⁻⁴cm·s⁻¹，Papp METO B-A = 0.25×10⁻⁴cm·s⁻¹，Papp 3TC B-A = 0.24×10⁻⁴cm·s⁻¹，Papp AZT B-A = 0.19×10⁻⁴cm·s⁻¹。
讨论
对于A-B方向，荧光素和美托洛尔的Papp结果分别显示低渗透性和高渗透性，表明该膜适用于渗透性研究。对于A-B方向，3TC和AZT的Papp结果表明，这些抗逆转录病毒药物的渗透率值接近美托洛尔。然而，对于B-A方向，Papp结果并未表明任何一种药物存在外排机制。因此，使用Franz扩散池的不同离体方法可以成功应用于药物渗透性研究，特别是用于药物生物药剂学分类。
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