PHARMACOKINETICS OF SPIRAMYCIN IN THE RHESUS-MONKEY - TRANSPLACENTAL PASSAGE AND DISTRIBUTION IN TISSUE IN THE FETUS

Transplacental transfer of spiramycin was investigated in a rhesus mon key model to study whether the antibiotic reaches therapeutic levels i n the fetus. Spiramycin concentrations were measured by bioassay and h igh-performance liquid chromatography. Pharmacokinetic parameters were determined for bioactive spiramycin as measured by the bioassay. Phar macokinetic pilot studies showed that spiramycin distribution follows a two-compartment model in rhesus monkeys. Following a single intraven ous dose of 50 or 250 mg, dose-dependent kinetics were observed. At a dose of 50 mg, 10% of the dose was excreted unchanged in the urine. At the higher dose of 250 mg, an oliguric effect was observed. Spiramyci n concentrations in fetal serum were measured over time while the mate rnal concentration was maintained at a constant level. During a 5-h ex periment, a maximum fetal-maternal serum ratio of 0.27 was found. In t hree fetuses, concentrations in serum and tissue were measured followi ng intravenous administration of 50 mg of spiramycin twice daily to th e mother for at least 7 days. The fetal-maternal serum ratios were fou nd to be 0.4 to 0.58 after intravenous administration of the final dos e of 50 mg to the mother. It appeared that spiramycin accumulated in t he soft tissues, especially in the liver and spleen, of both the mothe r and the fetus. The concentration in placental tissue appeared to be 10 to 20 times that of the concentration in fetal serum. The concentra tion of spiramycin in amniotic fluid was about five times higher than the concentration in fetal serum. Another important observation was th at absolutely no spiramycin was found in the brain.