Impact of an experimental PRRSV and Streptococcus suis coinfection on the pharmacokinetics of ceftiofur hydrochloride after intramuscular injection in pigs 1 D. N. DAY* J. W. SPARKS* L. A. KARRIKER* K. J. STALDER † L. W. WULF ‡ J. ZHANG § J. M. KINYON § M. L. STOCK ¶ R. GEHRING** C. WANG § J. ELLINGSON* & J. F. COETZEE ‡ *Swine Medicine Education Center, College of Veterinary Medicine, Iowa State Univer- sity, Ames, IA, USA; † Department of Ani- mal Science, Iowa State University, Ames, IA, USA; ‡ Pharmacology Analytical Support Team (PhAST), College of Veterinary Medi- cine, Iowa State University, Ames, IA, USA; § Veterinary Diagnostic and Production Ani- mal Medicine, College of Veterinary Medi- cine, Iowa State University, Ames, IA, USA; ¶ Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA; **Veterinary Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA Day, D.N., Sparks, J.W., Karriker, L.A., Stalder, K.J., Wulf, L.W., Zhang, J., Kinyon, J.M., Stock, M.L., Gehring, R., Wang, C., Ellingson, J., Coetzee, J.F. Impact of an experimental PRRSV and Streptococcus suis coinfection on the pharmacokinetics of ceftiofur hydrochloride after intramuscular injection in pigs. J. vet. Pharmacol. Therap. doi: 10.1111/jvp.12209. This study determined the impact of porcine reproductive and respiratory syndrome virus (PRRSV) and Streptococcus suis coinfection on the pharmaco- kinetic (PK) profile of ceftiofur hydrochloride in pigs after intramuscular (i.m.) injection. Eighteen clinically normal crossbred gilts were assigned by weight into a challenge group (10 pigs) and control group (eight pigs). Pigs in both groups received a single i.m. injection of ceftiofur hydrochloride (Excenel RTU Sterile Suspension; Zoetis) at a 5 mg/kg BW dose. Serial blood samples were collected to characterize the plasma concentration curve. After a 10 days drug washout period, the challenge group was inoculated with 2 mL of PRRSV isolate VR-2385 (10 5.75 50% tissue culture infective doses per mL) intranasally and 8 days later inoculated S. suis. When clinical disease was evident, the second PK assessment began in both challenge and control groups. Coinfected pigs demonstrated lower values of AUC and C MAX , but higher values of Cl/F and Vz/F indicating drug kinetics were altered by infec- tion. The data from this study have implications on ceftiofur treatment regi- mens in diseased pigs. (Paper received 22 September 2014; accepted for publication 16 January 2015) Locke Karriker, Swine Medicine Education Center, College of Veterinary Medicine, Iowa State University, 2227 Lloyd Vet Med Ctr, Ames, IA 50011, USA. E-mail: karriker@iastate.edu 1 Supported by the Swine Medicine Education Center and the Iowa State University Pharmacology Analytical Support Team. The assistance with data collection from Monique Pairis-Garcia, Brent Pepin, Christopher Sievers, Jillian LeKander, Caleb Robb, Nick Van Engen, Jay Lawrence, Marisa Rotolo, Paul Thomas, Levi Johnson, and Kurt Kuecker is acknowledged and greatly appreciated. INTRODUCTION Treatment regimens for drugs approved for use in swine are derived from pharmacokinetic (PK) studies completed in healthy pigs. There are few studies evaluating how disease impacts drug pharmacokinetics and the implications for modi- fying treatment regimens. One study which has been com- pleted demonstrated mean maximum plasma tetracycline concentration (C MAX ) was lower and achieved significantly later postadministration in pneumonic pigs relative to healthy pigs (Pijpers et al., 1991). In a second study, pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV) had decreased plasma ceftiofur concentrations relative to healthy pigs (Tantituvanont et al., 2009). PK studies in dis- eased animals better represent the circumstances where most drugs are applied in practice and will allow for modification of treatment regimens and drug withdrawal times in light of the altered physiologic status of diseased animals. Streptococcus suis is a bacterium which typically infects youn- ger pigs and commonly leads to a septicemia, meningitis, arthri- tis, endocarditis, and pneumonia (Gottschalk, 2012). Infection with PRRSV causes respiratory disease and reproductive failure, © 2015 John Wiley & Sons Ltd 1 J. vet. Pharmacol. Therap. doi: 10.1111/jvp.12209