人体中氧氟沙星的立体选择性代谢

Stereoselective metabolism of ofloxacin in human

５名健康志愿者日服单剂３００ｍｇ氧氟沙星［（±）－Ｏｆ１］后，采用立体选择性的ＲＰ－ＨＰＬＣ手性流动相添加剂法测定尿中Ｓ－（－）－Ｏｆ１和Ｒ－（＋）－Ｏｆ１浓度结果显示Ｏｆ１在人体内呈现立体选择性代谢。尿中排泄的Ｓ－（－）－Ｏｆ１／Ｒ－（＋）－Ｏｆ１之比随时间变化。服药后２ｈＳ／Ｒ是０．８７５，２４ｈ增加到１．１５０．Ｓ－（－）－Ｏｆ１的消除半衰期（ｔ１／２）是４．５７ｈ；消除速率常数（ｋ）是０．１５４ｈ；药时曲线下的面积（ＡＵＣ）为１．１７ｍｇ·ｈ－１．ｍＬ－１；Ｒ－（＋）－Ｏｆ１的ｔ１／２为４．１８ｈ，ｋ为０．１６８ｈ－１，ＡＵＣ是１．７８ｍｇ·ｈ－１·ｍＬ－１；经配对ｔ检验这三对参数间有显著性差异，Ｐ值分别小于０．０１，０．００１和０．００５．

The stereoselective metabolism of ofloxacin(Of1) was studied in healthy subjects after oral administrationof (±)-Of1 at a dose of 300 mg S-(-)-Of1 and R-(+)-Of1concentrations in urine were determined by RP-HPLC withchiral mobile phase additive. The ratio of SO to R-(+)enantiomer excretions increased with time. with S/ R ratioof 0.88 at 2 h and l. 15 at 24 h. The elimination half-life ofS form was 4.57 h, that was significantly greater (p<0.01)than that of R form (4.18 h). The elimination rate constant(k) of S-(-)-Of1 was lowcr than R(+)Of1. It was foundthat the disposition of Sand ROfl in human beingswas enantioselective although the difference in theirpharmacokinetic parameters was small.