Clinical Pharmacology of Cefazolin in Calves

The pharmacokinetic properties of cefazolin in the synovial fluid of the tibiotarsal joint were determined in 10 healthy mature cattle after intravenous regional injections of 250 mg cefazolin. A pneumatic tourniquet was positioned proximal to the tibiotarsal joint and the intravenous injection was performed distal to the tourniquet. Synovial fluid concentrations of cefazolin increased in the first 30 min and fluctuated between 54.7 +/- 11.0 micrograms/ml (mean +/- SEM) and 73.2 +/- 13.2 micrograms/ml in the following 90 min while the tourniquet remained inflated. After tourniquet removal, synovial fluid concentration-time curves followed first-order one-compartment model decay in most of the animals with an elimination half-life of 0.82 h (harmonic mean). Therapeutic concentrations of cefazolin in the synovial fluid of normal joints were reached and this injection technique could be used as an alternative to systemic administration of antibiotics to provide adequate concentrations in a localized area.

Section: Kesultssupporting

confidence: 79%

Section: Time (H)mentioning

confidence: 66%

See 1 more Smart Citation

Single‐dose pharmacokinetics of cefazolin in bovine synovial fluid after intravenous regional injection

Gagnon

Jg²,

Papich

et al. 1994

“…In calves the pharmacokinetic and anti-microbial features of cefoxitin appeared similar to those of the first-generation cephalosporin cefazolin (Soback et al, 1987). The longer half-life and larger volume of distribution would, however, favour the use of cefoxitin in treatment of calf diseases associated with pathogenic Gram-negative bacteria.…”

Section: Discussionmentioning

confidence: 90%

Pharmacokinetics of single doses of cefoxitin given by the intravenous and intramuscular routes to unweaned calves

Soback

1988

Self Cite

Cefoxitin pharmacokinetics and bioavailability were studied in unweaned calves. The antibiotic was administered to nine calves intravenously (i.v.), to seven calves intramuscularly (i.m.) at 20 mg/kg and to eight calves i.m. at 20 mg/kg together with probenecid at 40 mg/kg. Serum concentration versus time data were analysed using statistical moment theory (SMT). The i.v. data were also fitted by a linear, open two-compartment model. The elimination half-life (t1/2) was 66.9 +/- 6.9 min (mean +/- SD) after i.v. and 81.0 +/- 10.9 min after i.m. administration. The t1/2 increased to 125.5 +/- 15.6 min by the co-administration of probenecid. The total body clearance (ClT) was 4.88 +/- 1.71 ml/min/kg and the volume of distribution (Vss) 0.3187 +/- 0.0950 l/kg. The mean residence time (MRT) was 68.2 +/- 12.3 min after i.v. and 118.6 +/- 16.8 min after i.m. injection and increased to 211.5 +/- 16.8 min by the co-administration of probenecid. The mean absorption time (MAT) was 50.6 min and the estimated bioavailability (F) of cefoxitin after i.m. administration was 73.8%. The cefoxitin protein binding ranged from 55.0 to 42.0% at concentrations from 2 to 50 micrograms/ml. The MIC90 values for cefoxitin were 6.25 micrograms/ml for E. coli and Salmonella group B isolates, 3.13 micrograms/ml for Salmonella group C and D and Pasteurella multocida. There were no statistically significant differences between the pharmacokinetic parameters calculated by SMT or compartmental analysis. SMT provided an additional independent parameter, the MRT, for characterization of drug disposition kinetics.

“…Injection of anaesthetic agents in either the dorsal common digital vein or the abaxial proper plantar vein will produce anaesthesia to both deep and superficial tissues of the limb distal to the tourniquet ( Weaver, 1991). The successful use of regional intravenous perfusion of the limb with penicillin or oxytetracycline in a variety of clinical cases has been reported, and the authors’ impressions were that this technique decreased the expense and labour of treatment ( Hauck‐Bauer, 1977; Dietz et al ., 1980 ; Steiner et al ., 1990 ). More recently, synovial fluid concentrations of cefazolin following regional intravenous injection were evaluated ( Gagnon et al ., 1994 ).…”

Section: Introductionmentioning

confidence: 99%

Ceftiofur distribution in plasma and joint fluid following regional limb injection in cattle

Navarre

Zhang

Sunkara

et al. 1999

The objective of this study was to evaluate the efficacy of regional intravenous (i.v.) injection of ceftiofur in delivery of this drug to joint fluid and plasma in a limb distal to a tourniquet in five, healthy, adult, mixed breed beef cattle. A tourniquet was positioned in the mid-metacarpal region, and 500 mg of ceftiofur was administered through a catheter in the dorsal common digital vein (DCDV). Plasma samples were collected from the catheter at 15, 30 and 45 min postinjection, and from the abaxial proper palmar vein (APPV) at 15 min postinjection. Synovial fluid was collected from the metacarpal phalangeal joint at 45 min postinjection. Ceftiofur concentrations were estimated in plasma and synovial fluid using high-pressure liquid chromatography (HPLC) and a microbiological assay utilizing Pasteurella haemolytica as the test organism. Both assays indicated highest plasma concentrations of ceftiofur at 15 min, with the concentrations declining with time. Concentrations of ceftiofur in plasma obtained from the DCDV were not significantly different from APPV levels, indicating rapid distribution of ceftiofur within the limb. Microbiological assay always demonstrated higher concentrations of ceftiofur compared with HPLC assay, because the former probably also detected the active metabolites of ceftiofur as well as the parent compound. At 45 min, ceftiofur concentrations determined by HPLC were 251+/-97 and 15+/-5 microg/mL in plasma and synovial fluid, respectively. Regional intravenous injection appears to be a feasible technique to produce rapid distribution of ceftiofur within the limb well above therapeutic concentrations.