BIOAVAILABILITY OF SPIRAMYCIN AND LINCOMYCIN AFTER ORAL-ADMINISTRATION TO FED AND FASTED PIGS

The disposition of spiramycin and lincomycin was measured after intrav enous (i.v.) and oral (p.o.) administration to pigs. Twelve healthy pi gs (six for each compound) weighing 16-43 kg received a dose of 10 mg/ kg intravenously, and 55 mg/kg (spiramycin) or 33 mg/kg (lincomycin) o rally in both a fasted and a fed condition in a three-way cross-over d esign. Spiramycin was detectable in plasma up to 30 h after intravenou s and oral administration to both fasted and fed pigs, whereas lincomy cin was detected for only 12 h after intravenous administration and up to 15 h after oral administration. The volume of distribution was 5.6 +/- 1.5 and 1.1 +/- 0.2 L/kg body weight for spiramycin and lincomyci n, respectively. For both compounds the bioavailability was strongly d ependent on the presence of food in the gastrointestinal tract. For sp iramycin the bioavailability was determined to be 60% and 24% in faste d and fed pigs, respectively, whereas the corresponding figures for li ncomycin were 73% and 41%, The maximum plasma concentration of spiramy cin (C-max) was estimated to be 5 mu g/mL in fasted pigs and 1 mu g/mL only in fed pigs. It is concluded that an oral dose of 55 mg/kg body weight is not enough to give a therapeutically effective plasma concen tration of spiramycin against species of Mycoplasma, Streptoccocus, St aphylococcus and Pasteurella multocida. The maximum plasma concentrati on of lincomycin was estimated to be 8 mu g/mL in fasted pigs and 5 mu g/mL in fed pigs, but as the minimum inhibitory concentration for lin comycin against Actinobacillus pleuropneumoniae and P. multocida is hi gher than 32 mu g/mL a therapeutically effective plasma concentration could not be obtained following oral administration of the drug. For M ycoplasma the MIC90 is below 1 mu g/mL and a therapeutically effective plasma concentration of lincomycin was thus obtained after oral admin istration to both fed and fasted pigs.