Stability of Ester Prodrugs with Magnesium Oxide Using the Simple Suspension Method

抄録

The simple suspension method is a method of administering drugs via a feeding or gastrostomy tube, and it involves allowing tablets or capsules to be disintegrated and suspended in warm water at 55℃ without crushing. The present study evaluated the stability of two prodrugs suspended alone or in combination with an alkaline agent according to the simple suspension method. The study used two ester-prodrugs, acemetacin (AMT) and cefpodoxime proxetil (CPP), which are hydrolyzed at higher pH. Drug concentrations in the suspension were measured by high-performance liquid chromatography. AMT and CPP were not hydrolyzed when suspended alone, but decomposed under alkaline conditions with the addition of magnesium oxide (MgO). The AMT concentration decreased to 55.5％ and 38.9％ at 30 min and 60 min, respectively, whereas its active metabolite, indomethacin (IMT), increased from 0 to 90.7 µg/mL and 122.7 µg/mL at 30 and 60 min, respectively. The CPP concentrations with MgO were decreased to 47.9, 28.5, 20.8 and 12.7％ at 30, 60, 90, and 120 min, respectively. Therefore, AMT and CPP should not be administered in the simple suspension method in combination with an alkaline drug that increases the suspension pH.