BUCCAL ABSORPTION OF ENALAPRIL AND LISINOPRIL

Objective: The buccal absorption of captopril does not exhibit the cla ssical 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 resp onsible 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. Methods: The partitioning of enalapril and l isinopril into n-octanol was examined over the pH range of 3-9 at room temperature. Results: Enalapril exhibited maximal partitioning into t he organic phase at pH 4-5; minimal partitioning was recorded at pH va lues 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 partit ioning 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 partiti on coefficients, indicated that enalapril obeyed the normal lipid part ition hypothesis with respect to buccal absorption. The buccal absorpt ion of lisinopril also obeyed the lipid partition hypothesis over the pH range 3-7. These findings are in direct contrast to those for capto pril. The buccal partitioning experiments were repeated at the maximal pH for absorption for each angiotensin converting enzyme (ACE) inhibi tor, but with the addition of cephradine (0.05 mmol l(-1)). Conclusion : The data indicated that the presence of this peptide transport inhib itor had no effect on the buccal absorption of enalapril (0.06 mmol l( -1)) and lisinopril (0.057 mmol . l(-1)), which suggests that both dru gs do not share a common buccal absorption pathway with cephradine.