Shi Xiang-guo, Sun Yu-ming, Zhang Yu-feng, Zhong Da-fang
Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, China.
Acta Pharmacol Sin. 2004 Nov;25(11):1396-401.
To investigate the tissue distribution of bitespiramycin (BSPM) and spiramycin (SPM) in rats.
Liquid chromatographic-mass spectrometric assay was applied for the determination of three major components (isovalerylspiramycins, ISV-SPMs) of BSPM and their major active metabolites (SPMs) in rat tissues and plasma after an oral dose of bitespiramycin, as well as SPMs.
High levels of drug concentrations were observed in most tissues, especially in the liver, stomach, intestine, spleen, lung, womb, and pancreas. BSPM persisted long time in many rat tissues such that the drug concentration in spleen was 69.4 nmol/g at 60 h post-dose and it was still above the minimum inhibitory concentration of many susceptible pathogens. At 2.5 h post-dose, the total concentrations of ISV-SPMs and SPMs achieved in tissues were from 6 to 215 times higher than the corresponding concentrations in plasma. At 2.5 h post-dose, the mean C(t)/C(p) of BSPM appeared to be 2- or 3-fold those of SPM in most tissues. The tissue to plasma concentration ratios following oral dose of BSPM were higher than those of SPM in most tissues. The drug was not detected in brain and testis after a single dose of BSPM and SPM.
Both BSPM and SPM penetrate into rat tissues well and BSPM has higher tissue affinity than SPM.
研究必特螺旋霉素（BSPM）和螺旋霉素（SPM）在大鼠体内的组织分布。
采用液相色谱 - 质谱分析法，测定口服必特螺旋霉素后大鼠组织和血浆中必特螺旋霉素的三种主要成分（异戊酰螺旋霉素，ISV - SPMs）及其主要活性代谢产物（SPMs），以及螺旋霉素。
在大多数组织中观察到较高的药物浓度，尤其是在肝脏、胃、肠道、脾脏、肺、子宫和胰腺中。必特螺旋霉素在许多大鼠组织中持续时间较长，给药后60小时脾脏中的药物浓度为69.4 nmol/g，仍高于许多易感病原体的最低抑菌浓度。给药后2.5小时，组织中ISV - SPMs和SPMs的总浓度比血浆中相应浓度高6至215倍。给药后2.5小时，必特螺旋霉素在大多数组织中的平均C(t)/C(p)似乎是螺旋霉素的2至3倍。口服必特螺旋霉素后，大多数组织中药物的组织与血浆浓度比高于螺旋霉素。单次给药必特螺旋霉素和螺旋霉素后，在脑和睾丸中未检测到药物。
必特螺旋霉素和螺旋霉素均能很好地渗透到大鼠组织中，且必特螺旋霉素比螺旋霉素具有更高的组织亲和力。
