簡易懸濁時におけるACE阻害薬の安定性に対する酸化マグネシウムの影響

抄録

In the simple suspension method, the intended medicine is suspended in hot water when administered to a patient by tube. Suspension of the laxative, magnesium oxide is reported to hydrolyze ester-type drugs. Because several angiotensin converting enzyme (ACE) inhibitors have ester bonds in their structure, magnesium oxide may cause incompatibility when suspended with an ACE inhibitor. The purpose of this study was to clarify the effect of magnesium oxide on the stability of eight kinds of ACE inhibitors in the simple suspension method.

When suspended together with magnesium oxide in hot water (55℃), temocapril, delapril, captopril, and benazepril showed a significant decrease in concentration compared to when suspended alone. Enalapril, trandolapril, quinapril, and imidapril, however, showed no significant decrease. When temocapril was suspended with magnesium oxide, the concentration of its hydrolysis product temocaprilat was increased in a time-dependent manner. In addition, when temocapril was suspended in a carbonate-sodium bicarbonate buffer (pH 10.6), temocapril degradation was slower than with magnesium oxide, suggesting that the temocapril decomposition is not a simple hydrolysis caused only by pH but one requiring the presence of magnesium oxide as a catalyst.

Ester structures in ACE inhibitors are intended to improve gastrointestinal absorption. Therefore, the condition of several ACE inhibitors kept in suspension with magnesium oxide causes degradation of these drugs, inhibiting their absorption and pharmacological effects. It may be necessary for pharmacists to suggest to physicians that their prescriptions be changed to non-degradable ACE inhibitors and/or laxatives other than magnesium oxide.