2021 年 47 巻 11 号 p. 599-608
Patients with reduced swallowing function have difficulty taking tablets in their original form. In such cases, tablets are crushed (crushing method) and administered through feeding tubes, but this practice may affect efficacy. A simple suspension method (SSM) has been widely used to address issues of administering crushed tablets through feeding tubes. Most of all angiotensin-converting enzyme (ACE) inhibitors are ester prodrugs. When they are suspended with magnesium oxide, ester prodrugs are hydrolyzed, and the active metabolite increases before absorption. In this study, we investigated the effects of SSM and crushing methods on the pharmacokinetics of the ACE inhibitor using temocapril and magnesium oxide. A human clinical trial was conducted to compare the pharmacokinetics of temocapril and magnesium oxide in three groups in six healthy adult men (period 1, tablet group; period 2, SSM group; and period 3, crushing-and-mixed group). The pharmacokinetics of temocaprilat, which is the active metabolite, were examined. The AUC0-24 and Cmax of the SSM group were 89.3％ and 86.1％ compared with those of the tablet group, whereas those of the crushing-and-mixed group decreased to 73.0％ and 78.9％, respectively. In the crushing-and-mixed group, the concentration of temocapril decreased during crushing and long-term storage. Findings in the present study suggest that the crushing method may decrease in AUC0-24 and Cmax and that the expected drug effect may not be achieved. For ester prodrugs, the use of SSM might be considered rather than the crushing method.
