Pharmacokinetics in foremilk and antimicrobial activity of cephapirin following intramammary administration in healthy andStaphylococcus aureus-infected cows

Abstract

The intramammary administration of sodium cephapirin at 275 mg/quarter, twice every 12 hours in lactating cows resulted in higher drug concentrations in milk of quarters with no infection than in the subclinically infected ones. These concentrations were above the MIC90 for 35 hours in infected cows. According to these results intramammary administration of cephapirin at 12-hour intervals during lactation should be potentially effective against Staph. aureus infection, but studies of clinical efficacy are necessary for confirmation.

Pharmacokinetics and pharmacodynamics of intramammary cefquinome in lactating goats with and without experimentally induced Staphylococcus aureus mastitis

“…Lower concentrations of cefquinome were observed in skimmed milk of mastitic than healthy goats following IMM administration of 75 mg into one udder half. Our finding was consistent with previous reports for milk cefquinome concentrations of 138 ± 48 and 172 ± 41 µg/ml in mastitic and healthy cows, respectively (Zonca et al, ), milk cefoperazone concentrations of 310 ± 181 and 446 ± 287 µg/ml in mastitic and healthy cows, respectively (Cagnardi et al, ), and milk cephapirin concentrations of 235 ± 141 and 1,335 ± 1,323 µg/ml in mastitic and healthy cows, respectively (Cagnardi et al, ). We attribute part of the consistently lower concentrations of cefquinome found in milk after IMM treatment to breakdown in the blood–milk barrier.…”

“…Based on concentrations over time, the pharmacokinetics of cefquinome in milk from healthy goats was characterized by significantly greater area under concentration–time curve AUC and AUMC than in infected animals. A similar result was reported for cefquinome in cow's milk (Zonca et al, ), cephapirin in cow's milk (Cagnardi et al, ), and cefoperazone in cow's milk (Cagnardi et al, ). The variable degree of variation in the reduction of AUC as a result of infection is probably related to the severity of infection and consequently the disruption in mammary epithelial lining, thus confirming the uneven distribution of drugs in infected goats, as observed in previous studies (Cagnardi et al, ; Goutalier et al, ; Zonca et al, ).…”

“…The mean half‐life (T 1/2 ) in skimmed milk was shorter in mastitic goats than in healthy goats. In contrast, reduction of half‐lives of cefquinome, cephapirin, and cefoperazone between mastitic and healthy animals was smaller in goats than in cows (Cagnardi et al, ; Li et al, ; Zonca et al, ). The difference in results was most likely due to the higher volume of milk production in cows compared to goats that favors dilution of the antimicrobial and therefore a smaller flux across the milk blood barrier.…”

“…The results of the study reported here clearly demonstrate important differences in the pharmacokinetic values in skimmed milk and plasma between healthy and mastitic goats that associated with changes in residue risk. When taken into consideration with the results of other studies (El Badawy et al, ; Cagnardi et al, , ; Gehring & Smith, ; Goutalier, Combeau, Quillon, & Goby, ; Owens, Xiang, Ray, & Nickerson, ; Zonca et al, ), serious concerns must be raised about the clinical value of pharmacokinetic values such as C max , AUC, and K el determined in healthy animals for drugs that are intended to be administered to diseased animals. This highlights the need for performing pharmacokinetic studies in diseased animals.…”

“…A noncompartmental analysis was applied to the concentration–time data for each goat in skimmed milk and plasma following IMM infusion an IV bolus model as previously reported (Stockler et al, ) and extravascular model, respectively. The noncompartmental analysis was used for the concentration–time data following IMM infusion by other investigators (Cagnardi et al, ; Zonca et al, ). Based on concentrations over time, the pharmacokinetics of cefquinome in milk from healthy goats was characterized by significantly greater area under concentration–time curve AUC and AUMC than in infected animals.…”