氧氟沙星在肾功能障碍大鼠唾液中的分布

目的 :研究肾功能障碍时氧氟沙星 (OFLX)在唾液中分布的变化规律。方法 :通过 5 / 6肾摘除术 ,制成大鼠肾功能障碍模型 ,以模拟手术为对照。OFLX( 10mg·kg-1)静脉注射后 ,经时采血及腮腺 (Pr)、颌下腺 (M )唾液。采用HPLC法测定各样品中的OFLX浓度。结果 :肾功能障碍使大鼠OFLX血浆浓度显著增高 ,全身清除率下降约 4 0 %。肾障碍组Pr唾液中浓度明显增高 ,而M唾液中浓度与对照组之间差异无显著性。在肾功能障碍组及对照组 ,消失相的OFLX唾液中浓度及唾液 /血浆浓度比 (S/P比 ) ,在Pr唾液均比M唾液高约 2和 3倍。肾功能正常大鼠的S/P比与Pr唾液中药物浓度之间呈良好正相关。结论 :OFLX在大鼠唾液中的分布存在腺差。肾功能低下 ,导致了OFLX向Pr唾液中的移行性增大 ,但对M唾液的影响不明显。而OFLX向Pr唾液中分布的量与该唾液中药物浓度有关。

Distribution of ofloxacin into saliva in rats with renal failure

OBJECTIVE：To study the Pharmacokinetics of distribution of ofloxacin (OFLX) into saliva in rats with renal failure.METHODS：Blood,parotid and mandibular saliva were collected from the single-step 5/6th-nephrectomized and sham-operated (control) rats after bolus iv administration of OFLX (10 mg*kg-1).The concentrations of OFLX in these samples were determined by high-performance liquid chromatography.RESULTS：In the nephrectomized rats,significantly higher plasma OFLX levels were observed when compared with the control rats.Total body clearance decreased about 40% in the renal failure animals.At the terminal phase,both of the salivary levels and saliva/plasma concentration ratios of OFLX in parotid saliva were significantly higher about 2 or 3 times than those in mandibular in the both rats with normal or impaired renal function.In the rats with normal renal function,it was relationship existed between the saliva/plasma concentration ratios in parotid saliva and salivary concentration of OFLX.CONCLUSIONS：The results suggest that the gland-type difference in salivary excretion of OFLX exists in rats with normal or impaired renal function,and parotid salivary excretion of OFLX significantly elevated in the renal failure,animals but it did not influence on the mandibular saliva.The distribution of OFLX into parotid salivary was related to concentration of OFLX in this saliva.