Effect of Sucralfate on the Relative Bioavailability of Enrofloxacin and Ciprofloxacin in Healthy Fed Dogs

Background: Sucralfate impairs absorption of ciprofloxacin and other fluoroquinolones in humans, but no sucralfate-fluoroquinolone interaction has been reported in dogs. Veterinary formularies recommend avoiding concurrent administration of these medications, which might impact compliance, therapeutic success, and resistance selection from fluoroquinolones. Objectives: To determine whether a drug interaction exists when sucralfate is administered to fed dogs concurrently with ciprofloxacin or enrofloxacin, and whether a 2 hour delay between fluoroquinolone and sucralfate affects fluoroquinolone absorption. Animals: Five healthy Greyhounds housed in a research colony. Methods: This was a randomized crossover study. Treatments included oral ciprofloxacin (C) or oral enrofloxacin (E) alone, each fluoroquinolone concurrently with an oral suspension of sucralfate (CS, ES), and sucralfate suspension 2 hours after each fluoroquinolone (C2S, E2S). Fluoroquinolone concentrations were evaluated using liquid chromatography with mass spectrometry. Results: Drug exposure of ciprofloxacin was highly variable (AUC 5.52-22.47 h ?g/mL) compared to enrofloxacin (AUC 3.86-7.50 h ?g/mL). The mean relative bioavailability for ciprofloxacin and concurrent sucralfate was 48% (range 8-143%) compared to ciprofloxacin alone. Relative bioavailability of ciprofloxacin improved to 87% (range 37-333%) when sucralfate was delayed by 2 hours. By contrast, relative bioavailability for enrofloxacin and concurrent sucralfate was 104% (94-115%).Citation: KuKanich, K., KuKanich, B., Guess, S. and Heinrich, E. (2015), Effect of Sucralfate on the Relative Bioavailability of Enrofloxacin and Ciprofloxacin in Healthy Fed Dogs. Journal of Veterinary Internal Medicine. doi: 10.1111/jvim.1379

KSU Veterinary Health Center Joins ‘Everybody Counts’ to Serve Community Pets

This poster describes the collaborative efforts of the KSU Veterinary Health Center among many other community groups to provide healthcare services to families in need during the Everybody Counts event in Manhattan. At the 2019 Everybody Counts, we provided free veterinary examination, vaccines, de-worming, pet food, and more to over 80 pets in our community. Students directly benefit from hands-on clinical skills as the event, mentored by experienced clinicians while taking a medical history from pet owners, examining pets, drawing blood, or administering vaccinations. More than clinical experience, students learn about the importance of community engagement, listening to concerns of real pet owners, and our students become inspired to give back. Often veterinary students are sequestered between study carrels, lecture halls, our teaching hospital, and home, and this event brings a real and important perspective for them to consider within our veterinary profession. It gives names and faces to the less fortunate, and it reminds everyone how pets provide valuable companionship and that pets should not just be considered a luxury item. It also demonstrates that with fundraising and team work, we can make a difference for those in need. Students who participate in Everybody Counts come away with all of these skills and perspective, and with the motivation for future community engagement, asking what low-income pet owners in their hometowns need and how can they help

The challenge of evaluating pain and a pre-incisional local anesthetic block

Background. Our objective was to test the effectiveness of a local anesthetic line block administered before surgery in reducing postoperative pain scores in dogs undergoing ovariohysterectomy (OVHX).Methods. This study is a prospective, randomized, blinded, clinical trial involving 59 healthy female dogs. An algometric pressure-measuring device was used to determine nociceptive threshold, and compared to three subjective pain scales. Group L/B received a line block of lidocaine (4 mg/kg) and bupivacaine (1 mg/kg) subcutaneously in the area of the incision site and saline subcutaneously as premedication; group L/BM (positive control) received a similar block and morphine (0.5 mg/kg) subcutaneously for premedication; and group SS (negative control) received a saline line block and saline premedication. Criteria for rescue analgesia were defined before the study. Dogs were assessed prior to surgery, at extubation (time 0) and at 2, 4, 6, 8 and 24 h post-recovery. The data were analyzed with one-way ANOVA, and a Split Plot Repeated Measures ANOVA with one grouping factor and one repeat factor (time). P < 0.05 was considered statistically significant.Results. Approximately 33% of dogs required rescue analgesia at some point during the study, with no significant difference between groups. There was no significant difference between treatment groups with any assessment method.Conclusions. As there were no statistically significant differences between positive and negative controls, the outcome of this technique cannot be proven

Altered Plasma Pharmacokinetics of Ceftiofur Hydrochloride in Cows Affected with Severe Clinical Mastitis

Ceftiofur is the most commonly used antimicrobial in lactating dairy cows. Recently, there has been an increase in the number of violative residues of ceftiofur in the tissues of cull dairy cows. This was the first project in a series of projects we will be completing aimed at characterizing the pharmacokinetics of ceftiofur in disease challenged animals. The results of this study indicate that diseased animals have lower plasma concentrations and altered pharmacokinetics compared to healthy animals. Future work will investigate the influence of altered pharmacokinetics on the presence of violative residues

Treatment of acute pain in cats

The cat's popularity as a pet continues to grow, with the most recent surveys showing approximately 17% of the population live with cats. This increased popularity of cats invariably means that more cats are presented to veterinary surgeons for surgery and treatment of painful conditions, but it seems that the treatment of pain in the cat has lagged behind that of other species. Lack of analgesic administration may well stem from the difficulties in assessing pain in the cat, but is probably compounded by the false perceptions of the likelihood of severe side effects occurring more frequently with the use of opioids and non-steroidal anti-inflammatory drugs in cats, thereby inadvertently denying them the analgesics they require. This article complements a previous article covering the assessment of acute pain in the cat (White, 2016); the aim of this second article is to provide an evidence-based framework to follow for the treatment of acute pain in the cat

Parent-Metabolite Pharmacokinetic Models for Tramadol – Tests of Assumptions and Predictions

Allometric principles were used to discern cross-species differences in (±)-tramadol disposition and formation of its primary analgesic metabolite, (±)-O-desmethyl-tramadol (M1). Species differences in formation of M1 may help predict the analgesic effectiveness of tramadol. Tramadol was administered intravenously by a zero-order (constant infusion) process or rapid bolus dose and racemic concentrations of tramadol and M1 measured. Data were pooled to define differences between species (human, rat, cat, dog, goat, donkey and horse). A two-compartment linear disposition model with first-order elimination was used to describe tramadol and M1 disposition. Slow metabolizers were detected in 6% of the population and tramadol clearance to M1 was 16.2% that of extensive metabolizers. Tramadol clearance to M1 was slower and tramadol clearance by other pathways was faster in rats, dogs, and horses compared to humans. There are substantial differences between species in the pharmacokinetics of tramadol and its M1 metabolite, which are not explained by differences in body weight. The hypothesis that volumes of distribution are similar across species was shown not to be true. M1 exposure in the goat, donkey and cat was comparable to humans, which indicates it is likely to be an effective analgesic at typically used doses in these species but not in dogs or horses

Pharmacokinetics of meloxicam in mature swine after intravenous andoral administration

The purpose of this study was to compare the pharmacokinetics of meloxicam in mature swine after intravenous (IV) and oral (PO) administration. Six mature sows (mean bodyweight ± standard deviation = 217.3± 65.68 kg) were administered an IV or PO dose of meloxicam at a target dose of 0.5 mg/kg in a cross-over design. Plasma samples collected up to 48 hours post-administration were analyzed by high pressure liquid chromatography and mass spectrometry (HPLC-MS) followed by non-compartmental pharmacokinetic analysis. Mean peak plasma concentration (CMAX) after PO administration was 1070 ng/ml (645-1749 ng/ml). TMAX was recorded at 2.40 hour (0.50-12.00 hours) after PO administration. Half-life (T ½ λz) for IV and PO administration was 6.15 hours (4.39-7.79 hours) and 6.83 hours (5.18-9.63 hours) respectively. The bioavailability (F) for PO administration was 87% (39-351%). The results of the present study suggest that meloxicam is well absorbed after oral administration

Anti-inflammatory salicylate treatment alters the metabolic adaptations to lactation in dairy cattle

Citation:Farney, J. K., Mamedova, L. K., Coetzee, J. F., KuKanich, B., Sordillo, L. M., Stoakes, S. K., … Bradford, B. J. (2013). Anti-inflammatory salicylate treatment alters the metabolic adaptations to lactation in dairy cattle. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 305(2), R110–R117. https://doi.org/10.1152/ajpregu.00152.2013Adapting to the lactating state requires metabolic adjustments in multiple tissues, especially in the dairy cow, which must meet glucose demands that can exceed 5 kg/day in the face of negligible gastrointestinal glucose absorption. These challenges are met through the process of homeorhesis, the alteration of metabolic setpoints to adapt to a shift in physiological state. To investigate the role of inflammation-associated pathways in these homeorhetic adaptations, we treated cows with the nonsteroidal anti-inflammatory drug sodium salicylate (SS) for the first 7 days of lactation. Administration of SS decreased liver TNF-α mRNA and marginally decreased plasma TNF-α concentration, but plasma eicosanoids and liver NF-κB activity were unaltered during treatment. Despite the mild impact on these inflammatory markers, SS clearly altered metabolic function. Plasma glucose concentration was decreased by SS, but this was not explained by a shift in hepatic gluconeogenic gene expression or by altered milk lactose secretion. Insulin concentrations decreased in SS-treated cows on day 7 compared with controls, which was consistent with the decline in plasma glucose concentration. The revised quantitative insulin sensitivity check index (RQUICKI) was then used to assess whether altered insulin sensitivity may have influenced glucose utilization rate with SS. The RQUICKI estimate of insulin sensitivity was significantly elevated by SS on day 7, coincident with the decline in plasma glucose concentration. Salicylate prevented postpartum insulin resistance, likely causing excessive glucose utilization in peripheral tissues and hypoglycemia. These results represent the first evidence that inflammation-associated pathways are involved in homeorhetic adaptations to lactation.the transition from late pregnancy to lactation is a time of great physiological stress, especially for the dairy cow. The decline in feed intake that accompanies parturition, coupled with the rapid increase in energy requirements during lactogenesis, requires a dramatic shift in nutrient fluxes to release stored nutrients and direct them to the mammary gland. This programmed shift in metabolic setpoints is an archetypal example of homeorhesis, defined as the “coordinated changes in metabolism of body tissues necessary to support a physiological state” (4).Mechanisms underlying homeorhetic adaptions to lactation have been described to some extent. The somatotropic axis is decoupled during this time, resulting in dramatic elevations of plasma growth hormone concentrations without the expected rise in insulin-like growth factor 1 secretion (11, 51). Likewise, insulin sensitivity declines substantially from late gestation (5, 48). These endocrine shifts are critical for promoting the mobilization of stored nutrients and sparing glucose for use by the mammary gland. This conservation of glucose is particularly important in ruminants. The microbes that inhabit the rumen ferment most dietary carbohydrate to volatile fatty acids, leaving very little glucose to be absorbed in the small intestine. As a result, lactating cows absorb almost no glucose from the gastrointestinal tract and must synthesize as much as 5 kg of glucose in the liver daily (2).The homeorhetic adaptations that allow cows to increase milk production to 40 kg/day within days after parturition can stress the metabolic system. Rapid lipolysis can increase plasma nonesterified fatty acid (NEFA) concentrations by as much as 10-fold within a few days after parturition (21), and both hypoglycemia and hypocalcemia are common, as nutrients are drawn into the mammary gland. Ketosis and fatty liver (FL) are common metabolic diseases that result during this time; in fact, nearly 90% of all metabolic diseases in dairy cattle occur during the first 4 wk of the 305-day lactation (24).Despite their reliance on mobilized lipid as an energy source, dairy cattle entering lactation with greater adipose mass are at greater risk of developing metabolic diseases (34). It has become clear in the past decade that animals with excessive adiposity exhibit a low-grade inflammation (23), suggesting that perhaps inflammation underlies metabolic disturbances in obese dairy cows. In support of this hypothesis, cows with moderate or severe FL have increased levels of the inflammatory cytokine TNF-α (41). Inflammatory cytokines cause myriad metabolic changes in dairy cattle, including anorexia, lipomobilization, impaired insulin sensitivity, and reduced milk yield (7, 26, 27), all of which are associated with FL and ketosis. Furthermore, daily injection of TNF-α for 7 days increased liver triglyceride content independent of effects on feed intake, and this effect was accompanied by changes in hepatic gene expression consistent with both inflammation and a shift from fatty acid oxidation to triglyceride synthesis (8).These recent findings suggest that exogenous inflammatory agents are sufficient to induce metabolic dysfunction. Whether inflammation is a necessary causative factor in the natural progression of bovine FL and ketosis, however, remains unclear. To address this broad question, we used the nonsteroidal anti-inflammatory drug (NSAID) sodium salicylate (SS). Sodium salicylate is a weak inhibitor of cyclooxygenase (COX)-1 and COX-2 (31), and its probable mode of action is that it inhibits phosphorylation of the NF-κB inhibitor IκB-α (53). Phosphorylation of IκB results in its degradation, allowing NF-κB to be released for translocation into the nucleus and subsequent activation of an inflammatory transcription program (3). The specific hypothesis for this study was that SS would slow liver triglyceride accumulation, promote gluconeogenesis, and limit metabolic disease in dairy cows entering lactation. In contrast, our findings suggest that inflammatory signals may contribute to homeorhetic adaptations to lactation, especially regulation of glucose metabolism and modulation of lipolysis and ketogenesis as animals return to positive energy balance