Penetration of oxytetracycline into tissue‐cages in calves

The purpose of this study was to establish the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in the plasma and interstitial fluid (ISF) following subcutaneous (s.c.) administration of enrofloxacin. Ultrafiltration probes were placed in the s.c. tissue, gluteal musculature, and pleural space of five calves. Each calf received 12.5 mg/kg of enrofloxacin. Plasma and ISF samples were collected for 48 h after drug administration and analyzed by high pressure liquid chromatography. Plasma protein binding of enrofloxacin and ciprofloxacin was measured using a microcentrifugation system. Tissue probes were well tolerated and reliably produced fluid from each site. The mean +/- SD plasma half-life was 6.8 +/- 1.2 and 7.3 +/- 1 h for enrofloxacin and ciprofloxacin, respectively. The combined (ciprofloxacin + enrofloxacin) peak plasma concentration (Cmax) was 1.52 microg/mL, and the combined area under the curve (AUC) was 25.33 microg/mL. The plasma free drug concentrations were 54% and 81% for enrofloxacin and ciprofloxacin, respectively, and free drug concentration in the tissue fluid was higher than in plasma. We concluded that Cmax/MIC and AUC/MIC ratios for free drug concentrations in plasma and ISF would meet suggested ratios for a targeted MIC of 0.06 microg/mL.

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and tissue distribution of enrofloxacin and its active metabolite ciprofloxacin in calves

Davis¹,

Foster²,

Papich

2007

“…The penetration of antimicrobial agents into these various devices has been reviewed by Bergan (1981). The penetration of a broad range of antibiotics into a variety of devices has been demonstrated, including trimethoprim/sulfadiazine (Piercy, 1978) the cephalosporins (Peterson & Gerding, 1978;Holm et al, 1978;Tan & Salstrom, 1979;Adam et al, 1978), penicillins (Tan & Salstrom, 1979; Barza & Weinstein, 1974;Holm et al, 1978;Chisholm et al, 1973;Tight & White, 1980;Schreiner et al, 1981), aminoglycosides (Chisholm el al., 1973;Tan & Salstrom, 1979;Holm et al, 1978), tetracyclines (Bengtsson et al, 1986) and chloramphenicol (Ziv et al, 1983). Similar studies have also been conducted with antiinflammatory agents such as phenylbutazone and oxyphenbutazone (Lees et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

Distribution of cephapirin into a tissue chamber implanted subcutaneously in horses

Ce¹,

Beadle

Aranas³

et al. 1987

The pharmacokinetics of cephapirin sodium and its distribution into a tissue chamber implanted subcutaneously in the neck of mature horses are described. Cephapirin was administered as an intravenous bolus dose of 20 mg/kg. The serum concentration vs time curve was best described by a two-compartment open model. Cephapirin disappeared from serum rapidly (t1/2 beta = 18.8 min), and had only a modest volume of distribution (Vd(area) approximately equal to 346 mg/kg, Vd(ss) approximately equal to 204 ml/kg). Total clearance was also rapid (approximately equal to 13 ml/min.kg). Concentrations of the antibiotic in tissue chamber fluid, however, were quite constant from 30 min to 3 h post-injection, and did not decay in parallel with either the concentration of the drug in serum or the estimated concentration of drug in the peripheral compartment. The ratio of area under the curve (AUC0-3 h) for serum: chamber fluid was 13.8 : 1, while that for peripheral compartment : chamber fluid was 11 : 1. The slow rate of cephapirin transport into, and out of, the chamber may be related to its hydrophilic nature. The lack of parallelism between the chamber fluid decay curve and that of serum is characteristic of drugs with a very short half-life.

“…The tissue cage (TC) concept was used subsequently in large animal species by several authors (Higgins et al. , 1984; Bengtsson et al. , 1986; Clarke et al.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a tissue cage model of acute inflammation in the cat

Pelligand

House²,

Summers

et al. 2011

Four cylindrical silicon tissue cages (TC, internal volume: 6.7 ± 0.11 cm(3)) were inserted subcutaneously in 29 young healthy cats. A mild inflammatory reaction was induced by intracaveal injection of 1 mL of a 2%λ-carrageenan solution. TC exudate was subsequently sampled at predetermined times (up to 120 h) to measure exudate leucocyte counts and the concentrations of protein and eicosanoids. TC remained in situ for 9-10 months and were well tolerated. Leucocyte counts peaked at 34 h (50.1 ± 57.6 × 10(3) cells/mm(3) ) and returned towards baseline after 72 h. Protein concentration increased from 26.2 ± 2.7 g/L to a peak of 35.9 ± 6.0 g/L at 12 h before returning to baseline at 48 h. Exudate prostaglandin (PG)E(2) concentration peaked at 24 h (11.7 ± 13.7 ng/mL) and returned to baseline by 120 h. Repeated collection of fluid from noninjected cages did not increase transudate PGE(2). Ketoprofen (2 mg/kg, subcutaneously) suppressed exudate PGE(2) at 24 h. The carrageenan-stimulated TC model is an ethical and novel means of investigating soft tissue inflammation in the cat, in which exudate PGE(2) acts as surrogate marker of cyclooxygenase-2 activity. This model will facilitate the investigation of in vivo pharmacokinetics and pharmacodynamics of anti-inflammatory drugs in this species.