Abstract
Spiramycin (SPM) and acetylspiramycin (ASPM) have been known to be potent macrolide antibiotics in vivo, although spiramycins had rather mild antimicrobiol activities in vitro. The physiological disposition of SPMand ASPM could participate in their in vivo activities.
14C-labeled SPM-I or 8H-labeled ASPM was admini1s4tered intravenously in rats (20mg/kg), and plasma levels, excretion and tdistribution have been studied.The plasma levels of. SPM-I and ASPM were low both, in radioactivity and bioactivity. After intravenous administration, 14C-SPM-I was excreted by 48 hours into urine, bile and faeces at the rates of 39.6, 31.4%, and 37.1%, respectively. And 27.8% of the dose was recovered into urine by 48 hours after administration, of 8H-ASPM. Higher radioactivities were detected in the spleen, kidney cortex, submaxillary gland, liver and lung by whole body autoradiography 1 hour after intravenous administration, andth e levels tended to be retained until 24 hours.
After intravenous administration at the dose rate of 50mg/kg, the biological half-lives (T 1/2) of ASPM, SPM-I, josamycin and Mideeamycin were 151, 103, 71 minutes and 54 minutes, respectively, and the apparent volumes ofdi stibution (VβA) were 9.2, 8.9, 3.6 L/kg and 7.7 L/kg, respectively.
From these results, it was suggested that the highest activity observed for ASPM in experimental mice infec-tions might be correlated with high affinity for the tissues and the long biological half-life of ASPM.
