著者
清水 幸雄 柚原 亜美 矢野 勝子 北川 佳奈子 飯田 純一 五十嵐 信智 伊藤 清美 落合 和 折井 孝男 杉山 清
出版者
一般社団法人日本医療薬学会
雑誌
医療薬学 (ISSN:1346342X)
巻号頁・発行日
vol.36, no.1, pp.31-36, 2010 (Released:2011-12-24)
参考文献数
17
被引用文献数
6 4

There is concern about the possibility of degradation of the active substance as a result of pH changes when making suspensions of several drugs together by the simple suspension method.However,this has been investigated by few researchers.In the present study,we focused our attention on aspirin since it is known to be hydrolyzed at high temperatures or with elevation in pH.In this study,a Bufferin® 81 mg Tablet was suspended alone or together with alkaline drugs by the simple suspension method,and its stability evaluated.When in the suspension alone,the Bufferin® 81 mg Tablet was stable for 5 hours and the amount of salicylic acid (hydrolyte of aspirin) produced was negligible.On the other hand,when it was suspended together with alkaline agents (magnesium oxide tablet/powder,or lithium carbonate tablet),the residual content of aspirin decreased to 77-84% in ten minutes.The pH of the suspensions containing both the Bufferin® 81 mg Tablet and alkaline agents ranged from about 9 to 10 showing that alkalinity had been enhanced as compared with the suspension of Bufferin alone whose pH was 4.It has been reported that in low-dose aspirin therapy,platelet aggregation inhibition is unstable if the daily aspirin dosage is reduced to less than 75 mg.However for Bufferin® 81 mg Tablet,the results of the present study suggested that the beneficial effect of low-dose aspirin therapy might not be fully achieved it were suspended together with alkaline agents by the simple suspension method.
著者
石井 敬 戸田 雄大 五十嵐 信智 落合 和 杉山 清
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.132, no.3, pp.301-310, 2012 (Released:2012-03-01)
参考文献数
36
被引用文献数
2 14

Living organisms eliminate foreign low-antigenic substances, such as drugs and environmental pollutants, by detoxification mediated by metabolizing cytochrome P450 (CYP). We have examined the possible regulation of CYP expression by enteric bacteria. Cyp mRNA expression levels, Cyp3a protein expression level, and the activity of Cyp3a in hepatic microsomal fractions were compared in germ-free (GF) and specific pathogen-free (SPF) mice. We evaluated hepatic Cyp3a11 mRNA expression levels and Cyp3a metabolic activity in GF and SPF mice after five days of antibiotic administration. The fecal levels of lithocholic acid (LCA)-producing bacteria and hepatic taurolithocholic acid (TLCA) were also measured. Cyp mRNA expression levels, Cyp3a protein expression level, and the activity of Cyp3a in SPF mice were higher than those in GF mice, indicating that enteric bacteria increases hepatic Cyp3a expression. The effects of enteric bacteria-reducing antibiotics on Cyp3a expression were examined. We observed that decreasing enteric bacteria with antibiotics in SPF mice caused a significant decrease in the hepatic Cyp3a11 mRNA expression, TLCA, and fecal LCA-producing bacteria compared to the group that did not receive antibiotics. No change in Cyp3a11 expression was observed in GF mice that were treated with antibiotics. Administration of LCA to GF mice showed an increase in Cyp3a11 expression similar to that of SPF mice. The enzymes of the enteric bacteria are believed to metabolize and detoxify drugs by either reduction or hydrolysis. The results of this study indicate that changes in enteric bacteria may alter the expression and activity of hepatic drug metabolizing enzymes and pharmacokinetics. Therefore, enteric bacteria should be closely monitored to ensure the safe use of drugs.