Pharmacokinetics, PK/PD analysis and placental transfer of erythromycin administered to pregnant goats

Abstract

The aims of the present study were i) to characterize the pharmacokinetic of erythromycin (ERY) after intra venous (IV) and intramuscular (IM) administration to pregnant goats, ii) to make a PK/PD analysis by Monte Carlo simulation from steady-state pharmacokinetic parameters of ERY by IV and IM routes considering sensitivity of coagulase negative staphylococci isolate of milk of goats, and iii) to determine the placental transfer of the drug after intravenous maternal administration. Six pregnant goats (87–89 days of pregnancy) received ERY by the IV (10 mg/kg) and the IM (15 mg/kg) routes of administration. Blood samples were collected at predetermined times. The same animals (145–147 days of pregnancy) received a 10 mg/kg dose of erythromycin by IV route of administration and underwent a cesarean surgery; blood venous fetal and maternal samples were collected. ERY concentrations were determined by microbiological assay. MIC of one hundred and twenty seven coagulase negative staphylococci isolated from goats was determined by broth macrodilution method. ERY showed a wide distribution with low serum concentrations after IV and a high bioavailability after IM admin istration. PK/PD analysis by Monte Carlo simulation indicates that 15 mg/kg every 8 h IM administration of ERY in pregnant goats may be adequate for sensitive microorganisms with MIC ≤ 0.25 µg/mL. However, 10 mg/kg IV showed that does not meet the objective even for strains with MIC ≤ 0.125 µg/mL. Placental transfer of ERY was low (Concentrationfetus/Concentrationmother = 0.10).