Pharmacokinetics and tissue fluid distribution of cephalexin in the horse after oral and i.v. administration

The purpose of this study was to determine the pharmacokinetics and tissue fluid distribution of cephalexin in the adult horse following oral and i.v. administration. Cephalexin hydrate (10 mg/kg) was administered to horses i.v. and plasma samples were collected. Following a washout period, cephalexin (30 mg/kg) was administered intragastrically. Plasma, interstitial fluid (ISF) aqueous humor, and urine samples were collected. All samples were analyzed by high-pressure liquid chromatography (HPLC). Following i.v. administration, cephalexin had a plasma half-life (t(1/2)) of 2.02 h and volume of distribution [V(d(ss))] of 0.25 L/kg. Following oral administration, the average maximum plasma concentration (C(max)) was 3.47 mug/mL and an apparent half-life (t(1/2)) of 1.64 h. Bioavailability was approximately 5.0%. The AUC(ISF):AUC(plasma) ratio was 80.55% which corresponded to the percentage protein-unbound drug in the plasma (77.07%). The t(1/2) in the ISF was 2.49 h. Cephalexin was not detected in the aqueous humor. The octanol:water partition coefficient was 0.076 +/- 0.025. Cephalexin was concentrated in the urine with an average concentration of 47.59 microg/mL. No adverse events were noted during this study. This study showed that cephalexin at a dose of 30 mg/kg administered orally at 8 h dosage intervals in horses can produce plasma and interstitial fluid drug concentrations that are in a range recommended to treat susceptible gram-positive bacteria (MIC < or = 0.5 microg/mL). Because of the low oral bioavailability of cephalexin in the horse, the effect of chronic dosing on the normal intestinal bacterial flora requires further investigation.     

Infection with Menangle virus in flying foxes (Pteropus spp.) in Australia

Objective To examine flying foxes (Pteropus spp.) for evidence of infection with Menangle virus. Design Clustered non‐random sampling for serology, virus isolation and electron microscopy (EM). Procedure Serum samples were collected from 306 Pteropus spp. in northern and eastern Australia and tested for antibodies against Menangle virus (MenV) using a virus neutralisation test (VNT). Virus isolation was attempted from tissues and faeces collected from 215 Pteropus spp. in New South Wales. Faecal samples from 68 individual Pteropus spp. and four pools of faeces were examined by transmission EM following routine negative staining and immunogold labelling. Results Neutralising antibodies (VNT titres ≥ 8) against MenV were detected in 46% of black flying foxes (P. alecto), 41% of grey‐headed flying foxes (P. poliocephalus), 25% of spectacled flying foxes (P. conspicillatus) and 1% of little red flying foxes (P. scapulatus) in Australia. Positive sera included samples collected from P. poliocephalus in a colony adjacent to a piggery that had experienced reproductive disease caused by MenV. Virus‐like particles were observed by EM in faeces from Pteropus spp. and reactivity was detected in pooled faeces and urine by immunogold EM using sera from sows that had been exposed to MenV. Attempts to isolate the virus from the faeces and tissues from Pteropus spp. were unsuccessful. Conclusion Serological evidence of infection with MenV was detected in Pteropus spp. in Australia. Although virus‐like particles were detected in faeces, no viruses were isolated from faeces, urine or tissues of Pteropus spp.     

Elimination of salicylic acid in goats and cattle

Sodium salicylate was administered to cattle and goats IV and PO according to a crossover design. Total urinary excretion of SA and its metabolites was measured for 3 days after dosing. Salicyluric acid (SUA) was the only metabolite detected in urine of either species. Recovery of sodium salicylate and SUA in goats amounted to 67.9 and 34.6% of the dose, respectively, after IV administration. After oral dosing, total recoveries were 30.2% (sodium salicylate) and 71.7% (SUA) of dose. By comparison, cattle excreted significantly (P less than 0.05) less sodium salicylate (54.0%) and more SUA (49.9%) after IV dosing. The same pattern was observed after oral administration, wherein cattle excreted less than 12% as sodium salicylate and more than 99% as SUA. In both species, almost 90% of the drug excreted as sodium salicylate was found in urine within the first 12 hours after an IV dose and within 24 hours after oral dosing. The excretion of SUA was somewhat slower in both species, especially after oral administration. The data suggested that there were only quantitative differences in the metabolism and elimination of sodium salicylate between the 2 species, with cattle excreting a higher proportion of the drug as the glycine conjugate SUA.     

The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses

Davis, J. L., Marshall, J. F., Papich, M. G., Blikslager, A. T., Campbell, N. B. The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses. J. vet. Pharmacol. Therap. 34 , 12–16. The purpose of this study was to determine the pharmacokinetics of deracoxib following oral administration to horses. In addition, in vitro equine whole blood cyclooxygenase (COX) selectivity assays were performed. Six healthy adult horses were administered deracoxib (2 mg/kg) orally. Plasma samples were collected prior to drug administration (time 0), and 10, 20, 40 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after administration for analysis with high pressure liquid chromatography using ultraviolet detection. Following PO administration, deracoxib had a long elimination half‐life (t_1/2k₁₀) of 12.49 ± 1.84 h. The average maximum plasma concentration (C_max) was 0.54 μg/mL, and was reached at 6.33 ± 3.44 h. Bioavailability was not determined because of the lack of an IV formulation. Results of in vitro COX selectivity assays showed that deracoxib was selective for COX‐2 with a COX‐1/COX‐2 ratio of 25.67 and 22.06 for the IC₅₀ and IC₈₀, respectively. Dosing simulations showed that concentrations above the IC₈₀ for COX‐2 would be maintained following 2 mg/kg PO q12h, and above the IC₅₀ following 2 mg/kg PO q24h. This study showed that deracoxib is absorbed in the horse after oral administration, and may offer a useful alternative for anti‐inflammatory treatment of various conditions in the horse.     

Drugs and the liver

The authors discuss the liver's influence on drug disposition in the body and the influence of drugs on the liver. Drug-induced hepatotoxicity with regard to mechanisms and causative agents is discussed, as well as administration of drugs to patients with existing liver disease.     

Strategies to reduce feedlot cattle heat stress: effects on tympanic temperature

Three experiments were conducted to evaluate the effect of different management strategies on body temperature of feedlot steers finished in the summer months. In Exp. 1, 24 crossbred steers were chosen to assess the effect of altered feed intake and feeding time on tympanic temperature (TT) response. Managed feeding (MF) treatments were applied for 22 d only and provided 1) ad libitum access to feed at 0800 (ADLIB), 2) feed at 1600 with amount adjusted so that no feed was available at 0800 (BKMGT), 3) feed at 1600 at 85% of predicted ad libitum levels (LIMFD). During heat stress conditions on d 20 to 22 of MF, LIMFD and BKMGT had lower (P < 0.05) TT than ADLIB from 2100 through 2400. A carryover effect of limit-feeding was evident during a severe heat episode (d 36 to 38) with LIMFD steers having lower (P < 0.05) TT than ADLIB. In Exp. 2, TT were obtained from 24 crossbred steers assigned to three treatments, consisting of no water application (CON), water applied to feedlot mound surfaces from 1000 to 1200 (AM) or 1400 to 1600 (PM). From 2200 to 0900 and 1200 to 1400, steers assigned to morning sprinkling treatment had lower (P < 0.05) TT than steers assigned to afternoon sprinkling treatment. In Exp. 3, 24 steers were utilized in a 2 x 2 factorial arrangement of treatments with factors of feeding time [0800 (AMF) and 1400 (PMF)] and sprinkling (WET and DRY). Tympanic temperatures were monitored under hot environmental conditions on d 30 to 32 and 61 to 62. A feeding time x sprinkling interaction (P < 0.001) was evident on d 30 to 32, although AMF/DRY steers had the highest (P < 0.05) TT. On d 61 to 62, TT of PMF steers was higher (P < 0.05) than AMF between 1500 to 1800. Use of sprinklers can effectively reduce TT of feedlot cattle, whereas shifting to an afternoon vs morning feeding time was most beneficial when bunks were empty several hours prior to feeding.     

The relationship of insulin-like growth factor-I with postweaning performance in Angus beef cattle

This study was designed to evaluate the ontogeny of serum IGF-I (SI) concentrations and its relationship to animal performance in a 140-d postweaning feeding trial. Ninety-eight progeny representing six sires (three high and three low feed conversion) and two sexes (43 bulls and 55 heifers) with ad libitum access to feed were allocated by sire and sex to monitor individual weights and pen feed consumption. Blood serum samples were obtained at the beginning of test (average age of 230 d) and every 28 d thereafter until each animal reached a fat thickness (estimated by sonoray) of 8.9 mm. Individual serum samples were acid-ethanol extracted and measured for IGF-I peptide by heterologous RIA. Serum IGF-I concentrations differed (P less than .10) between high (H) and low (L) feed conversion progeny groups at the end of the first 28-d period (125.12 vs 89.52 ng/ml) and tended to differ at the conclusion of the second 28-d period (P less than .15). Weight gains of H and L groups tended to differ in the second and third 28-d periods (P = .11 and .10, respectively). Serum IGF-I concentrations differed (P less than .05) between bulls and heifers for the first through fourth 28-d periods (P less than .01, P less than .05, P less than .10 and P less than .01, respectively). Phenotypic correlations indicated that pens with higher mean SI concentrations at the beginning of the test consumed less feed and had lower cumulative feed:gain ratios.(ABSTRACT TRUNCATED AT 250 WORDS)     

Goitrous hypothyroidism associated with treatment with trimethoprim-sulfamethoxazole in a young dog

CASE DESCRIPTION: A 16-week-old female Boxer that had been treated for 5 weeks with trimethoprim-sulfamethoxazole and chloramphenicol because of aspiration pneumonia was evaluated for bilaterally symmetric masses in the subcutaneous tissues of the ventral neck, in the region of the larynx. CLINICAL FINDINGS: Fine-needle aspirates were obtained from the neck masses; cytologic examination revealed well-differentiated thyroid epithelial tissue. A blood sample was collected for serum biochemical and thyroid function analyses. Mild hyperphosphatemia, severe hypercholesterolemia, mild hyperkalemia, and a mild increase in creatine kinase activity were identified. Serum concentration of total thyroxine was less than the lower reference limit, and that of thyroid-stimulating hormone was greater than the upper reference limit. Findings were consistent with a diagnosis of clinical hypothyroidism in a skeletally immature dog. TREATMENT AND OUTCOME: Treatment with trimethoprim-sulfamethoxazole was discontinued. The dog was reevaluated 3 weeks later, at which time the neck masses were markedly decreased in size. Serum concentrations of cholesterol and potassium were lower; serum concentrations of total thyroxine and thyroid-stimulating hormone were near or within respective reference ranges. Age-appropriate increases in serum phosphorus concentration and serum alkaline phosphatase activity were also detected. CLINICAL RELEVANCE: To the authors' knowledge, this is the first report of antimicrobial-induced goiter in a dog. Cytologic examination of fine-needle aspirates and interpretation of data from serum biochemical and thyroid function analyses were needed to obtain a definitive diagnosis. Practitioners should include goiter among the differential diagnoses for ventral neck swellings in young dogs receiving potentiated sulfonamide antimicrobials.     

Evaluation of intramuscular butorphanol, azaperone, and medetomidine and nasal oxygen insufflation for the chemical immobilization of white-tailed deer, Odocoileus virginianus

Chemical immobilization of wildlife often includes opioids or cyclohexamines. These substances are problematic as a result of their required storage, handling, and record-keeping protocols. A potentially useful alternative sedation protocol includes a combination of butorphanol, azaperone, and medetomidine (BAM: 0.43 mg/kg butorphanol, 0.36 mg/kg azaperone, 0.14 mg/kg medetomidine). One risk of wildlife immobilization with any drug combination is hypoxemia. This may be of particular importance when using an alpha 2 agonist such as medetomidine because of its powerful vasoconstrictive effect. In this prospective study, the BAM combination was evaluated for chemical immobilization of white-tailed deer. Additionally, selected physiologic parameters associated with BAM immobilization, including oxygen saturation via pulse oximetry and arterial blood gas measurement, with and without nasal insufflation of oxygen at a relatively low flow of 3 L/min, were evaluated. The BAM combination resulted in a predictable onset of sedation, with a mean induction time to lateral recumbency of 9.8 +/- 3.6 min. All deer recovered smoothly within a range of 5-20 min after reversal with intramuscular administration of naltrexone, atipamazole, and tolazoline (NAT). Clinically relevant decreases in arterial partial pressure of oxygen (PaO2) and oxygen saturation (SpO2) were observed in animals not receiving supplemental oxygen, while both parameters significantly improved for oxygen-supplemented deer. Pulse oximetry with this protocol was an unreliable indicator of oxygen saturation. In this study, altitude, recumbency, hypoventilation, butorphanol- and medetomidine-specific effects, as well as the potential for alpha 2 agonist-induced pulmonary changes all may have contributed to the development of hypoxemia. Overall, capture of white-tailed deer with the BAM/NAT protocol resulted in excellent chemical immobilization and reversal. Because the BAM combination caused significant hypoxemia that is unreliably detected by pulse oximetry but that may be resolved with nasal oxygen insufflation, routine use of oxygen supplementation is recommended.