丙酰螺旋霉素的药理研究

PHARMACOLOGICAL STUDY ON PROPIONYLSPIRAMYCIN

丙酰螺旋霉素(Pro-SPM)为一抗革兰氏阳性球菌为主的新抗生素,体内外药效优于乙酰螺旋霉素(Ac-SPM),急性毒性较小,小鼠LD_(50)口服为3700mg/kg,静脉为354.96mg/kg,大鼠LD_(50)口服为4000mg/kg。Pro-SPM 30mg/kg静脉注射对兔心电图、呼吸无影响,仅引起轻度血压下降。Pro-SPM在兔体内的代谢与Ac-SPM相似,均转变成螺旋霉素,药动学参数提示Pro-SPM的体内代谢慢于Ac-SPM,Pro-SPM的达峰浓度(Cmax)、曲线下面积(AUC)均高于Ac-SPM。兔口服Pro-SPM、Ac-SPM后24小时回收率分别为5.52%、5.25%。Pro-SPM的Ames试验、染色体畸变试验结果均为阴性。

Propionylspiramycin(Pro-SPM),a new antibiotic,is active against gram- positive bacteria.It is more active in vivo and in vitro than spiramycin,Its acute oral LD_(50) in mice and in rats are 3700mg/kg and 4000mg/kg respectively.The acute intravenous LD_(50)in mice is 354.96mg/kg.Following intravenous injection 30mg/kg of the drug in rab- bits did not affect the animal′s electrocardiogram and respiration but the blood pressure of the animal was slightly reduced.The metabolic character of the drug and acetylspiramycin (Ac-SPM)in rabbits are similar and spiramycin is the metabolite.The pharmacokinetic parameter suggested that:the metabolic rate is faster with Ac-SPM than with Pro-SPM; the peak concentration and the area under concentration-time curve of Ac-SPM and Pro-SPM in rabbits are higher with Pro-SPM than with Ac-SPM.The urinary recoveries within 24 hrs.following oral administration of Ac-SPM and Pro-SPM in rabbits are 5.25% and 5.53% respectively.Ames test and chromosome distortion test were carried out with negative results.