2017 年 77 巻 3 号 p. 177-185
This study aims to develop a method to investigate the usefulness of oral drug formulation in the exploratory clinical study performed at the microdose level (MD clinical study). As model drugs, erythromycin and simvastatin were used and enteric-coated pills (for erythromycin) and sustained release pills (for simvastatin) were prepared at the MD level. In the MD clinical study, solution and MD formulation of both drugs were orally administered to healthy subjects (n=8) according to the crossover study protocol. Plasma concentrations of the drug were determined using the ultra-high sensitive analytical method with liquid chromatography/tandem mass spectrometry. The lower limit of quantification in the plasma sample was 2.0 pg/mL for both drugs. In the case of erythromycin, area under the plasma concentration time curve (AUC) obtained with an enteric-coated MD formulation was markedly higher than that with solution, indicating that the effect of enteric-coated formulation to prevent degradation in the stomach can be evaluated even at the MD level. In the case of simvastatin, sustained release pills delayed the plasma profile of the drug compared to the solution due to the delay in the absorption, while AUC values were not significantly different. This result suggested that the plasma profile of simvastatin can be controlled by the sustained release formulation without any decrease in the absorbed amount. In conclusion, MD clinical study with an appropriate formulation is a useful tool to evaluate the feasibility of new drug candidates to be developed as oral drug products.
