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标题：Effects of Aluminium-Containing Antacid on Bioavailability of Ofloxacin Following Oral Administration of Pivaloyloxymethyl Ester of Ofloxacin as Prodrug
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作者：Yorinobu MAEDA ; Kei OMODA ; Toshio KONISHI 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1993
卷号：16
期号：6
页码：594-599
DOI：10.1248/bpb.16.594
出版社：The Pharmaceutical Society of Japan
摘要：We newly synthesized a pivaloyloxymethyl ester of ofloxacin (OFLX-PVM) as prodrug in order to avoid the chelate formation between new quinolone and metal cations such as Al³⁺, Mg²⁺, Ca²⁺, or Fe²⁺ in the gastrointestinal tract. This compound was rapidly hydrolyzed in an incubation experiment by 43% in plasma, by 92% in small intestinal mucosal homogenates, and by 97% in liver homogenates during 0.5 h incubation, but was resistant to hydrolysis by pancreatic enzymes. In everted gut sac experiments, this compound was efficiently absorbed even in the presence of aluminium ion, whereas the absorption of ofloxacin (OFLX) was decreased significantly by the presence of aluminium ion. Minimal inhibitory concentration (MIC) values of OFLX-PVM were far higher than OFLX. Effects of aluminium hydroxide on the oral bioavailability of OFLX and OFLX-PVM were investigated in rabbits. The area under the plasma concentration-versus-time curve from zero to 24 h (AUC_{0-24 h}) following oral administration of OFLX was decreased significantly by 47.6% by combined administration with aluminium hydroxide, but AUC_{0-24 h} values of OFLX-PVM coadministered with and without aluminium hydroxide were similar to that of OFLX alone.These observations indicate that this new compound is likely to offer a prodrug for avoidance of interaction between new quinolone and metal cations.
关键词：new quinolone;ofloxacin;pivaloyloxymethyl ester;metal cation;prodrug;absorption