Pharmacokinetics of ampicillin and sulfadimidine in pigs infected experimentally with Streptococcus suum

Twenty-three hybrid pigs (23 +/- 3 kg body wt) were assigned to three groups to investigate the pharmacokinetics of ampicillin (APC, 10 mg/kg) administered intravenously (i.v.) and intramuscularly (i.m.), and sulfadimidine (SDM, 50 mg/kg) administered intravenously as a bolus injection. In the first series of experiments the animals remained healthy. Subsequently, the pigs were infected with Streptococcus suum by subcutaneous (s.c.) inoculation and the experiments were repeated. The total apparent distribution volume of APC given intravenously was increased from 0.512 +/- 0.026 L/kg in uninfected pigs to 0.68 +/- 0.06 L/kg (P < 0.01) in infected pigs, whereas there were no significant changes in the same parameter for SDM (P > 0.05). The clearance of APC was increased markedly from 0.52 +/- 0.07 L/kg/h in uninfected pigs to 0.62 +/- 0.10 L/kg/h in infected pigs. In contrast, SDM clearance was decreased markedly from 0.023 +/- 0.003 L/kg/h to 0.017 +/- 0.003 L/kg/h (P < 0.05). As a result, the biological half-lives of the drugs were altered to varying degrees in infected pigs. The half-life of SDM was increased from 15.0 +/- 3.0 h in uninfected pigs to 20 +/- 7h in infected pigs (P < 0.05), but differences in APC half-lives between uninfected and infected animals were not observed (P > 0.05). There were no statistically significant differences in pharmacokinetic parameters of APC administered by intramuscular injection between the healthy and the diseased status, although its half-life was shortened from 0.76 +/- 0.22 h in the healthy to 0.57 +/- 0.23 h in the diseased. The results suggest that blood concentrations of APC and SDM are affected differently by the same disease due to its specific effects on their distribution and elimination.