OBJECTIVE To compare the plasma pharmacokinetics of tulathromycin between 3-week-old (preweaned) and 6-month-old (weaned) calves and to characterize the distribution of tulathromcyin into pulmonary epithelial lining fluid (PELF) and interstitial fluid (ISF) of preweaned and weaned calves following SC administration of a single dose (2.5 mg/kg). ANIMALS 8 healthy 3-week-old and 8 healthy 6-month-old Holstein steers. PROCEDURES A jugular catheter and SC ultrafiltration probe were aseptically placed in the neck of each calf before tulathromycin administration. Blood, ISF, and bronchoalveolar lavage fluid samples were collected at predetermined times before and after tulathromycin administration for quantification of drug concentration. A urea dilution method was used to estimate tulathromycin concentration in PELF from that in bronchoalveolar lavage fluid. Tulathromycin–plasma protein binding was determined by in vitro methods. Plasma pharmacokinetics were determined by a 2-compartment model. Pharmacokinetic parameters and drug concentrations were compared between preweaned and weaned calves. RESULTS Clearance and volume of distribution per fraction of tulathromycin absorbed were significantly greater for weaned calves than preweaned calves. Tulathromycin–plasma protein binding was significantly greater for weaned calves than preweaned calves. Maximum PELF tulathromycin concentration was significantly greater than the maximum plasma and maximum ISF tulathromycin concentrations in both groups. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that age affected multiple pharmacokinetic parameters of tulathromycin, likely owing to physiologic changes as calves mature from preruminants to ruminants. Knowledge of those changes may be useful in the development of studies to evaluate potential dose adjustments during treatment of calves with respiratory tract disease.

OBJECTIVE To evaluate pharmacokinetics of cefazolin after IV injection of cefazolin (22 mg/kg) and after simultaneous IV and IM injections of cefazolin (total dose, 44 mg/kg) to dogs. ANIMALS 12 adult Beagles. PROCEDURES Dogs (6/group) were assigned to receive a single injection of cefazolin (IV group; 22 mg/kg, IV) or simultaneous injections (IV + IM group; 22 mg/kg, IV, and 22 mg/kg, IM). Interstitial fluid was collected over a 5-hour period by use of ultrafiltration probes for pharmacokinetic analysis. RESULTS Mean cefazolin concentration in the interstitial fluid at 1, 1.5, 2, 3, 4, and 5 hours after injection was 39.6, 29.1, 21.2, 10.3, 6.4, and 2.7 μg/mL, respectively, for the IV group and 38.3, 53.3, 46.4, 31.7, 19.1, and 8.9 μg/mL, respectively, for the IV + IM group. Mean area under the concentration-time curve extrapolated to infinity, maximum concentration, half-life, and time to maximum concentration was 74.99 and 154.16 h·μg/mL, 37.3 and 51.5 μg/mL, 0.96 and 1.11 hours, and 1.28 and 1.65 hours, respectively, for the IV and IV + IM groups. CONCLUSIONS AND CLINICAL RELEVANCE Cefazolin concentrations in interstitial fluid of dogs were maintained at > 4 μg/mL for 4 hours after a single IV injection and for 5 hours after simultaneous IV and IM injections. Therefore, simultaneous IV and IM administration of cefazolin 30 to 60 minutes before surgery should provide interstitial fluid concentrations effective against the most common commensal organisms (Staphylococcus spp and Streptococcus spp) on the skin of dogs for surgical procedures lasting ≤ 4 hours.

OBJECTIVE To assess the pharmacokinetic properties of cefovecin in a cold-water teleost species. ANIMALS 10 healthy adult copper rockfish (Sebastes caurinus), sex unknown. PROCEDURES Cefovecin (16 mg/kg) was administered SC to the rockfish. Blood samples were collected at predetermined points for measurement of plasma cefovecin concentrations (3 samples/fish). Plasma cefovecin concentrations were measured via liquid chromatography with mass spectrometry. Pharmacokinetic analysis was performed by means of naïve pooled analysis and compartmental modeling. Plasma protein binding of cefovecin was determined by ultrafiltration. RESULTS Cefovecin administration appeared to be well tolerated by the rockfish. Pharmacokinetic analysis resulted in a maximum plasma concentration of 104.8 μg/mL at 2.07 hours after administration. Plasma terminal half-life was 32.5 hours, and area under the curve was 5,132 h·g/mL. Plasma protein binding was low (< 10%) for plasma concentrations of 10 and 100 μg of cefovecin/mL when assessed at 7.8° and 20°C. Plasma concentrations > 1 μg/mL persisted for the full 7-day follow-up period. CONCLUSIONS AND CLINICAL RELEVANCE SC administration of cefovecin to copper rockfish at a dose of 16 mg/kg yielded plasma concentrations > 1 μg/mL that persisted to 7 days, but some interindividual variability was observed. The low degree of plasma protein binding but high circulating concentration of free drug may allow an extended administration interval in rockfish. Studies are needed to assess the efficacy and safety of this dose in rockfish.

Objective-To estimate pharmacokinetic variables and measure tissue fluid concentrations of meropenem after IV and SC administration in dogs. Animals-6 healthy adult dogs. Procedure-Dogs were administered a single dose of meropenem (20 mg/kg) IV and SC in a crossover design. To characterize the distribution of meropenem in dogs and to evaluate a unique tissue fluid collection method, an in vivo ultrafiltration device was used to collect interstitial fluid. Plasma, tissue fluid, and urine samples were analyzed by use of high-performance liquid chromatography. Protein binding was determined by use of an ultrafiltration device. Results-Plasma data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean +/- SD values for half-life, volume of distribution, and clearance after IV administration for plasma samples were 0.67 +/- 0.07 hours, 0.372 +/- 0.053 L/kg, and 6.53 +/- 1.51 mL/min/kg, respectively, and half-life for tissue fluid samples was 1.15 +/- 0.57 hours. Half-life after SC administration was 0.98 +/- 0.21 and 1.31 +/- 0.54 hours for plasma and tissue fluid, respectively. Protein binding was 11.87%, and bioavailability after SC administration was 84%. Conclusions and Clinical Relevance-Analysis of our data revealed that tissue fluid and plasma (unbound fraction) concentrations were similar. Because of the kinetic similarity of meropenem in the extravascular and vascular spaces, tissue fluid concentrations can be predicted from plasma concentrations. We concluded that a dosage of 8 mg/kg, SC, every 12 hours would achieve adequate tissue fluid and urine concentrations for susceptible bacteria with a minimum inhibitory concentration of 0.12 µg/mL.

Unbound or free cortisol constitutes a small fraction of total plasma cortisol, but is believed to represent the biologically active portion of this circulating glucocorticoid. We tested the hypothesis that the percentage free cortisol was altered in plasma from dogs with hyperadrenocorticism, which could account for a greater target tissue response to this circulating hormone. The percentage free cortisol in plasma samples from human beings, healthy dogs, and dogs with hyperadrenocorticism was estimated, using centrifugal ultrafiltration-dialysis. Total cortisol concentrations were determined by use of radioimmunoassay. Total cortisol concentrations appeared greater in plasma from human beings than in plasma from either group of dogs. However, the percentage free cortisol was lower in plasma from human beings, resulting in a calculated concentration of free cortisol that was quite similar between plasma from human beings and healthy dogs. Total plasma cortisol concentrations were greater (P < 0.01) in samples from dogs with hyperadrenocorticism (190 +/- 113 nmol/L; mean +/- SD) than in healthy dogs (102 +/-85 nmol/L), but the percentage free cortisol was not different between these 2 groups (dogs with hyperadrenocorticism, 16 +/- 9%; healthy dogs, 13 +/- 6%). However, plasma free cortisol concentrations (product of total and the percentage of free cortisol) were greater (P < 0.01) in samples from dogs with hyperadrenocorticism (36 +/- 41 nmol/L) than in those from healthy dogs (16 +/- 9 nmol/L). Significant (P < 0.001) positive linear relationships were found between total cortisol concentrations and percentage free cortisol in plasma samples from healthy dogs and dogs with hyperadrenocorticism. Furthermore, the slope of these lines was not different between the 2 groups, providing no evidence for alterations in cortisol binding associated with hyperadrenocorticism. The higher total cortisol concentrations in dogs affected with this disease do, however, result in greater concentrations of free cortisol in circulation, contributing to the development of clinical signs observed in this disease.

Bovine fibroblast interferon (BoF-IFN), produced in primary bovine embryonic kidney cell cultures after priming and infection with bluetongue virus, was purified by controlled pore glass (CPG) chromatography to a specific activity of 10(6) U/mg of protein, with 40% recovery of the original activity. The crude IFN was concentrated more than sevenfold during purification. This proved to be a relatively simple, practical method of obtaining sufficient quantities of partially purified natural BoF-IFN for further studies. The CPG-purified BoF-IFN was further concentrated by sequential ultrafiltration and was analyzed by sodium dodecyl sulfate/polyacrylamide-gel electrophoresis (SDS-PAGE). Interferon, recovered from denaturing conditions either by dialysis against phosphate-buffered saline solution or by dilution in cell culture medium containing 10% fetal bovine serum, migrated as a single stainable protein with molecular weight of 21,000 on analytic SDS-PAGE gels. Recovered IFN activity from preparative SDS-PAGE totalled 8.7% of that applied. Attempts to further pruify CPG-purified BoF-IFN by zinc chelate affinity chromatography were unsuccessful.