Stability and in vitro absorption of captopril, enalapril and lisinopril across the rat intestine.
In vitro absorption of three angiotensin converting enzyme (ACE) inhibitors, captopril, enalapril and lisinopril, and their stabilities in aqueous buffer as well as their resistance to intestinal and dermal tissue homogenates were investigated. The results demonstrate that the spontaneous oxidation of captopril, enalapril and lisinopril followed first-order degradation kinetics in McIlvaine's citrate-phosphate buffer. The degradation rates for enalapril and lisinopril were much slower than that for captopril. With the former two ACE inhibitors, the first-order rate constants of breakdown in the presence of dermal homogenate were not significantly different from the control values. Intestinal homogenate increased the decomposition of both of these inhibitors when compared to the enzyme-free control systems. On the other hand, the first-order rates of disappearance of captopril in the presence of both dermal and intestinal homogenates were lower than in the enzyme-free system. The extent of reduction was proportional to the amount of homogenate added. This suggests that tissue homogenates prevent the oxidation of captopril to its disulphide dimer. Transport experiments show that the amounts of ACE inhibitors transferred from solution on the mucosal side increased linearly with incubation time over the 2 hr of study. The rates of transfer from the mucosal side to the serosal side had the following rank order: captopril > enalapril > lisinopril roughly in the ratio 1:1.13:1.27. Addition of harmaline caused a significant reduction in the transfer rate of captopril compared to the control system, which strongly suggests that captopril is transported by a sodium-dependent carrier-mediated process across intestinal tissue.
Zhou
X H
XH
Drug Delivery Research Group, School of Pharmacy, Queen's University of Belfast, U.K.
Li Wan Po
A
A
D000818:Animals; D001693:Biological Transport, Active; D002216:Captopril / Q000378:metabolism*; D004355:Drug Stability; D004656:Enalapril / Q000378:metabolism*; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics; D017706:Lisinopril / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism
D004656:Enalapril; D002216:Captopril; D017706:Lisinopril