McElnay J C, Al-Furaih T A, Hughes C M, Scott M G, Elborn J S, Nicholls D P
Pharmacy Practice Research Group, School of Pharmacy, The Queen's University of Belfast, Northern Ireland, UK.
Eur J Clin Pharmacol. 1998 Oct;54(8):609-14. doi: 10.1007/s002280050522.
The buccal absorption of captopril does not exhibit the classical pH/partition hypothesis, suggesting that mechanisms other than passive diffusion are involved in its absorption; animal studies have suggested that a peptide carrier-mediated transport system may be responsible for its absorption. The present study evaluated the effects of pH on octanol partitioning, and on the buccal absorption of enalapril and lisinopril, using in vitro techniques and buccal partitioning in human volunteer subjects.
The partitioning of enalapril and lisinopril into n-octanol was examined over the pH range of 3 9 at room temperature.
Enalapril exhibited maximal partitioning into the organic phase at pH 4 5; minimal partitioning was recorded at pH values 8 and 9. The partitioning of lisinopril into n-octanol was found to be maximal at pH 9 and minimal at pH 3. Using the buccal absorption technique, the partitioning of enalapril and lisinopril (0.5 mg), was examined in six healthy male volunteers from buffered solutions (pH 3, 4, 5, 6, 7, 8 and 9). In the case of enalapril, lowest buccal partitioning occurred at pH 3, 8 and 9, while maximal partitioning occurred at pH 5; absorption of lisinopril was not extensive at any pH, but was greatest at pH 6. These results, in addition to the n-octanol partition coefficients, indicated that enalapril obeyed the normal lipid partition hypothesis with respect to buccal absorption. The buccal absorption of lisinopril also obeyed the lipid partition hypothesis over the pH range 3-7. These findings are in direct contrast to those for captopril. The buccal partitioning experiments were repeated at the maximal pH for absorption for each angiotensin converting enzyme (ACE) inhibitor, but with the addition of cephradine (0.05 mmol x l(-1)).
The data indicated that the presence of this peptide transport inhibitor had no effect on the buccal absorption of enalapril (0.06 mmol x l(-1)) and lisinopril (0.057 mmol x l(-1)), which suggests that both drugs do not share a common buccal absorption pathway with cephradine.
卡托普利的颊部吸收并不遵循经典的pH/分配假说，这表明除被动扩散外的其他机制参与了其吸收过程；动物研究表明，一种肽载体介导的转运系统可能负责其吸收。本研究使用体外技术和人体志愿者的颊部分配实验，评估了pH对依那普利和赖诺普利的正辛醇分配以及颊部吸收的影响。
在室温下，研究了pH值为3至9范围内依那普利和赖诺普利在正辛醇中的分配情况。
依那普利在pH 4至5时进入有机相的分配量最大；在pH值为8和9时记录到的分配量最小。发现赖诺普利在正辛醇中的分配在pH 9时最大，在pH 3时最小。使用颊部吸收技术，在6名健康男性志愿者中，研究了依那普利和赖诺普利（0.5毫克）在缓冲溶液（pH 3、4、5、6、7、8和9）中的分配情况。对于依那普利，在pH 3、8和9时颊部分配最低，而在pH 5时分配最大；赖诺普利在任何pH值下吸收都不广泛，但在pH 6时最大。这些结果，除了正辛醇分配系数外，表明依那普利在颊部吸收方面遵循正常的脂质分配假说。赖诺普利在pH 3至7范围内的颊部吸收也遵循脂质分配假说。这些发现与卡托普利的情况形成直接对比。在每种血管紧张素转换酶（ACE）抑制剂吸收的最大pH值下重复颊部分配实验，但添加了头孢拉定（0.05 mmol·L⁻¹）。
数据表明，这种肽转运抑制剂的存在对依那普利（0.06 mmol·L⁻¹）和赖诺普利（0.057 mmol·L⁻¹）的颊部吸收没有影响，这表明这两种药物与头孢拉定不共享共同的颊部吸收途径。
