Infection with Porcine Reproductive and Respiratory Syndrome Virus and Streptococcus suis changes the pharmacokinetics of ceftiofur hydrochloride in swine

摘要

Treatment regimens for drugs approved for use in swine are derived from pharmacokinetic (PK) studies completed in healthy pigs. There are few studies examining the impact of disease on pharmacokinetics, and these studies have evaluated a limited number of drugs in few species. The same pharmacokinetic parameters were not uniformly affected between studies, however, a commonality exists that disease impacts pharmacokinetics. The pharmacokinetics of ceftiofur hydrochloride has been broadly investigated in clinically normal pigs, but information on the pharmacokinetics in Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and Streptococcus suis co-infected pigs has not been reported.Original research was conducted to provide additional information on how disease affects the PK profile of ceftiofur hydrochloride, a commonly used antimicrobial in swine. A PRRSV and Streptococcus suis coinfection model was selected due to the common occurrence of this coinfection in the field, its significant impacts on production, and lack of effective Streptococcus suis control measures. Study results revealed the pharmacokinetic profile of ceftiofur was altered by disease. Coinfected pigs demonstrated a decrease in AUC and a reduction in CMAX, but showed an increase in Cl/F and a higher Vz/F. These alterations have implications on treatment regimens when using ceftiofur products, as lower plasma concentrations and higher clearance rates reduce the likelihood of achieving effective plasma levels relative to Streptococcus suis MICs in the presence of PRRS virus.There remains a need for continuing research to evaluate the impact of disease on pharmacokinetics. Research should focus on evaluating different disease models and antimicrobial classes, as well as identifying the mechanism behind these changes. Information gained needs to be included in the drug approval process to ensure the most efficacious dosing regimens are labeled for their respective disease indication.