Comparative pharmacokinetics using a microbiological assay and high performance liquid chromatography following intravenous administration of cefquinome in lactating goats with and without experimentally induced Staphylococcus aureus mastitis

Abstract

Cefquinome pharmacokinetic values were compared using a microbiological assay (MA) and high performance liquid chromatography (HPLC) in lactating goats with and without experimentally induced Staphylococcus aureus mastitis. Five healthy lactating goats received an IV injection of cefquinome sulfate (75mg, equivalent to cefquinome at 3.0mg/kg BW). The same dose of cefquinome sulfate was administered IV after clinical mastitis was induced by intracisternal infusion of 100 cfu of S. aureus ATCC 29213. Jugular venous blood and milk samples were obtained periodically after cefquinome administration in healthy and mastitic goats, and plasma and skimmed milk cefquinome concentrations were determined using MA and HPLC. Deming regression and Bland-Altman plots indicated equivalence of MA and HPLC. Both MA and HPLC analytical methodologies yielded statistically similar mean values for the cefquinome concentration-time relationship in plasma and skimmed milk and similar values for almost all calculated pharmacokinetic indices; however, HPLC had a lower limit of quantification LOQ and coefficient of variation, and a higher correlation coefficient for standard curves. Noncompartmental pharmacokinetic (PK) analysis indicated that mastitis decreased the mean residence time of cefquinome in plasma but did not change the mean residence time in skimmed milk. Skimmed milk cefquinome concentrations after IV injection remained below the MIC (0.25μg/mL) for S. aureus at every measurement time except at 6h after injection, and clinical mastitis remained present for at least 5 days in treated goats. In conclusion, MA provides a simple, practical and inexpensive method for measuring cefquinome concentrations in plasma and skimmed milk samples from goats, while, HPLC proved to be more sensitive, specific and accurate. Mastitis increased cefquinome clearance compared to healthy goats which emphasizes the importance of performing pharmacokinetic studies in infected animals. Additional studies are required to determine whether intramammary cefquinome is effective in treating S. aureus mastitis in goats.