Pharmacokinetics of gentamicin in mares in late pregnancy and early lactation

The disposition of drugs may differ between pregnant and nonpregnant animal s, necessitating a change in dosage. We hypothesized that volume of distrib ution or clearance may be different for aminoglycoside antibiotics in pregn ant mares vs. nonpregnant lactating mares. To examine this hypothesis, we a dministered gentamicin sulfate to seven Thoroughbred and Quarterhorse mares on two occasions, followed by plasma drug gentamicin assay and pharmacokin etic analysis. The first dose was administered 1-4 weeks before parturition (mean weight 578 kg) and the second dose was administered in the period 1- 4 weeks after parturition (mean weight 518 kg). The dose administered at ea ch time was approximately 6.6 mg/kg, intravenously (i.v.). Plasma gentamici n concentrations were determined using fluorescence polarization immunoassa y and pharmacokinetic analysis was performed using a two-compartment open m odel. The plasma concentration vs. time profiles and total area-under-the-c urve were almost identical for mares at late gestation vs. early lactation. Mean volume of distribution at steady-state was 0.15 (+/- 0.02) and 0.16 ( +/- 0.03) L/kg, systemic clearance was 1.06 (+/-0.17) and 1.11 (+/- 0.17) m L/kg/min, and mean (harmonic) elimination half-life was 2.2 and 2.1 h, for pregnant and nonpregnant mares, respectively We concluded that there were n o differences in drug distribution and clearance between pregnant and nonpr egnant lactating mares. Gentamicin was also assayed in plasma of newborn fo als after an injection of 6.6 mg/kg to three of the mares within 60 min of parturition. Gentamicin was undetectable in plasma samples from these foals and, therefore, apparently does not cross the placenta of mares at term.