title: Tissue distribution of bitespiramycin and spiramycin in rats.
abstract: OBJECTIVE
  To investigate the tissue distribution of bitespiramycin (BSPM) and spiramycin (SPM) in rats.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Both BSPM and SPM penetrate into rat tissues well and BSPM has higher tissue affinity than SPM.
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, China.
authors.forename: Xiang-guo
authors.initials: XG
authors.lastname: Shi
authors.forename: Yu-ming
authors.initials: YM
authors.lastname: Sun
authors.forename: Yu-feng
authors.initials: YF
authors.lastname: Zhang
authors.forename: Da-fang
authors.initials: DF
authors.lastname: Zhong
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015572:Spiramycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D015572:Spiramycin; C423662:carrimycin