Comparative pharmacokinetics of phenylbutazone in healthy young-adult and geriatric horses.

OBJECTIVE: To evaluate the effects of aging on phenylbutazone (PBZ) disposition in older horses (≥ 25 years old) compared to young adults (4 to 10 years old) by characterizing the pharmacokinetic profile of PBZ and its active metabolite, oxyphenbutazone (OPBZ), following a 2.2-mg/kg dose, IV. We hypothesized that the disposition of PBZ will be affected by age. ANIMALS: 16 healthy horses (8 young adults aged 4 to 10 years and 8 geriatric horses ≥ 25 years old). METHODS: Horses were administered a single 2.2-mg/kg PBZ dose, IV. Plasma samples were collected at designated time points and frozen at -80 °C until assayed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analyses were performed using Phoenix WinNonlin, version 8.0 (Certara). Both clinical and pharmacokinetic data were compared between age groups using independent samples t tests, with P < .05 considered significant. RESULTS: Baseline characteristics did not differ between groups, with the exception of age, weight, and plasma total solids. Plasma concentrations of PBZ were best described by a two-compartment model. The maximum plasma concentration of OPBZ was reached at 5 hours for both age groups, and the metabolite-to-parent-drug area-under-the-curve ratios were approximately 20% for both groups. None of the pharmacokinetic parameters of PBZ or its metabolite, OPBZ, differed significantly between age groups. CLINICAL RELEVANCE: The hypothesis was rejected as there was no significant difference in PBZ disposition in young-adult horses compared to geriatric horses. Our data do not support the need for dose adjustments of PBZ in clinically healthy geriatric horses.

A CONSORT-guided, randomized, double-blind, controlled pilot clinical trial of inhaled lidocaine for the treatment of equine asthma.

There are limited options for treatment of the common disease, equine asthma. The aim of this study was to estimate the feasibility and potential efficacy of using nebulized lidocaine for treating equine asthma, while at the same time treating a separate cohort of asthmatic horses with inhaled budesonide. Nineteen horses with a history consistent with equine asthma were recruited from our referral population for a double-blind, randomized, controlled pilot clinical trial using Consolidated Standards of Reporting Trials (CONSORT) guidelines. After screening, 16 horses met the inclusion criteria for equine asthma and 13 horses actually completed the study. Horses were treated by their owners at home for 14 d before returning to our hospital for follow-up assessment. Interventions consisted of nebulization q12h for 14 d with 1.0 mg/kg body weight (BW) of lidocaine or corticosteroid treatment (nebulized budesonide 1 µg/kg, q12h). Clinical and tracheal mucus score, pulmonary function testing, and respiratory secretion cytology were assessed after 2 weeks of treatment to determine the outcome. Both lidocaine and budesonide cohorts had significant decreases (P < 0.05) in clinical score; the lidocaine cohort showed a significant decrease in bronchoalveolar lavage (BAL) neutrophil percentage and tracheal mucus score. Neither treatment resulted in significant changes in lung function parameters. No adverse events occurred. Lidocaine may be an effective and safe treatment for equine asthma in horses that cannot tolerate treatment with corticosteroids.

Il existe des options limitées pour le traitement de la maladie répandue, l'asthme équin. Le but de cette étude était d'estimer la faisabilité et l'efficacité potentielle de l'utilisation de la lidocaïne nébulisée pour traiter l'asthme équin, tout en traitant en même temps une cohorte distincte de chevaux asthmatiques avec du budésonide inhalé. Dix-neuf chevaux ayant des antécédents compatibles avec l'asthme équin ont été recrutés dans notre population de référence pour un essai clinique pilote contrôlé, randomisé, en double aveugle, conformément aux directives CONSORT (Consolidated Standards of Reporting Trials). Après dépistage, 16 chevaux répondaient aux critères d'inclusion de l'asthme équin et 13 chevaux ont terminé l'étude. Les chevaux ont été traités par leurs propriétaires à domicile pendant 14 jours avant de retourner à notre hôpital pour une évaluation de suivi. Les interventions consistaient en une nébulisation deux fois par jour pendant 14 jours avec 1,0 mg/kg de poids corporel (PC) de lidocaïne ou un traitement aux corticostéroïdes (budésonide nébulisé 1 µg/kg, q12h). Le score clinique et de mucus trachéal, les tests de la fonction pulmonaire et la cytologie des sécrétions respiratoires ont été évalués après 2 semaines de traitement pour déterminer le résultat. Les cohortes de lidocaïne et de budésonide présentaient des diminutions significatives (P < 0,05) du score clinique; la cohorte de lidocaïne a montré une diminution significative du pourcentage de neutrophiles du lavage bronchoalvéolaire (BAL) et du score de mucus trachéal. Aucun des deux traitements n'a entraîné de changements significatifs dans les paramètres de la fonction pulmonaire. Aucun événement indésirable n'est survenu. La lidocaïne peut être un traitement efficace et sûr de l'asthme équin chez les chevaux qui ne tolèrent pas le traitement aux corticostéroïdes.(Traduit par Docteur Serge Messier).

Clinical effects and pharmacokinetics of nebulized lidocaine in healthy horses.

Background: Nebulized lidocaine appears promising as a novel corticosteroid-sparing therapeutic for equine asthma, but its safety and pharmacokinetic behavior have yet to be confirmed. Objective: To describe the effect of nebulized lidocaine on upper airway sensitivity, lung mechanics, and lower respiratory cellular response of healthy horses, as well as delivery of lidocaine to lower airways, and its subsequent absorption, clearance, and duration of detectability. Animals: Six healthy university- and client-owned horses with normal physical examination and serum amyloid A, and no history of respiratory disease within 6 months. Methods: Prospective, descriptive study evaluating the immediate effects of 1 mg/kg 4% preservative-free lidocaine following nebulization with the Flexineb®. Prior to and following nebulization, horses were assessed using upper airway endoscopy, bronchoalveolar lavage, and pulmonary function testing with esophageal balloon/pneumotachography and histamine bronchoprovocation. Additionally, blood and urine were collected at predetermined times following single-dose intravenous and nebulized lidocaine administration for pharmacokinetic analysis. Results: Upper airway sensitivity was unchanged following lidocaine nebulization, and no laryngospasm or excessive salivation was noted. Lidocaine nebulization (1 mg/kg) resulted in a mean epithelial lining fluid concentration of 9.63 ± 5.05 µg/mL, and a bioavailability of 29.7 ± 7.76%. Lidocaine concentrations were higher in epithelial lining fluid than in systemic circulation (Cmax 149.23 ± 78.74 µg/L, CELF:Cmaxplasma 64.4, range 26.5-136.8). Serum and urine lidocaine levels remained detectable for 24 and 48 h, respectively, following nebulization of a single dose. Baseline spirometry, lung resistance and dynamic compliance, remained normal following lidocaine nebulization, with resistance decreasing post-nebulization. Compared to the pre-nebulization group, two additional horses were hyperresponsive following lidocaine nebulization. There was a significant increase in mean airway responsiveness post-lidocaine nebulization, based on lung resistance, but not dynamic compliance. One horse had BAL cytology consistent with airway inflammation both before and after lidocaine treatment. Conclusions: Nebulized lidocaine was not associated with adverse effects on upper airway sensitivity or BAL cytology. While baseline lung resistance was unchanged, increased airway reactivity to histamine bronchoprovocation in the absence of clinical signs was seen in some horses following nebulization. Further research is necessary to evaluate drug delivery, adverse events, and efficacy in asthmatic horses.

Diagnosis and management of Enterococcus spp infections during rehabilitation of cold-stunned Kemp's ridley turtles (Lepidochelys kempii): 50 cases (2006-2012).

OBJECTIVE: To evaluate clinical data for cold-stunned Kemp's ridley turtles (Lepidochelys kempii) with Enterococcus spp infections during rehabilitation. DESIGN: Retrospective case series. ANIMALS: 50 stranded cold-stunned Kemp's ridley turtles hospitalized between 2006 and 2012. PROCEDURES: Medical records for turtles from which Enterococcus spp were isolated were reviewed retrospectively, and clinical data, including morphometric data, body temperature at admission, physical examination findings, antimicrobial medication history, history of medications administered IV, environmental data, day of diagnosis, clinical signs at diagnosis, microbiological testing results, sources of positive culture results, hematologic and plasma biochemical data, cytologic and histopathologic results, radiographic findings, antimicrobial treatments, time to first negative culture result, treatment duration, results of subsequent cultures, and case outcome, were collated and analyzed. RESULTS: Enterococcus spp were isolated from bacteriologic cultures of blood, bone, joint, and respiratory tract samples and a skin lesion, with supporting evidence of infection provided by histopathologic, cytologic, and radiographic data. Positive culture results were associated with clinical problems such as lethargy, anorexia, and lameness. Most (34/43 [79%]) turtles for which an antemortem diagnosis was made survived with treatment and were released into the wild. CONCLUSIONS AND CLINICAL RELEVANCE: Cold-stunned Kemp's ridley turtles may be affected by serious Enterococcus spp infections during rehabilitation. Recognition and treatment of these infections are important for successful rehabilitation.

Using Raman spectroscopy in tablet moisture surface analysis: tablet surface markers.

A method was developed to monitor the hydration of a tablet surface using chemical functional groups able to bind atmospheric water through H-bonding. In this study, generic oral dissolving loratadine tablets were used. These tablets have relatively high mannitol and lactose concentrations. Both mannitol and lactose have C-OH alcohol functional groups, several of which are potentially available for H-bonding with atmospheric water. The Raman intensity of the alcohol functional groups decreases upon hydration. This observation can be used to indirectly monitor water adsorbed to tablet surfaces at the alcohol sites. The hydration assay is based on the change in the Raman peak intensity of the alcohol C-OH stretching at 875.5 cm(-1). Consequently the decrease in the Raman intensity of this vibration can be used to monitor water adsorption. The Raman measurement of tablet surface water was compared to the direct moisture measurement method using a microbalance. The Raman spectroscopy is used to monitor the water that is specifically bound to the C-OH alcohol functional groups available for hydration. The microbalance was used to monitor the tablets' weight change during water adsorption and desorption. The distribution of the ratio of the Raman intensity of C-OH peak at 875.5 cm(-1) divided by the intensity of loratadine's C-Cl peak at 712.6 cm(-1) was experimentally determined to be a Gaussian distribution with a mean of 3.22+/-0.277. Raman analysis indicates that there is both tightly and loosely bound water at the tablet surface. This can be a useful technique with regard to inspecting and controlling the tablet drying process.

The role and education of the veterinary pharmacist.

OBJECTIVE: To define the role and education of the traditional pharmacist who supports the needs of the veterinarian (hereafter referred to as veterinary pharmacist) and a pharmacist who practices solely in veterinary pharmacy (here after referred to as veterinary pharmacy specialist). METHODS: The Delphi technique involving 7 panels of 143 experts was employed to reach consensus on the definition of the roles and education of the veterinary pharmacist and veterinary pharmacy specialist. RESULTS: The veterinary pharmacy specialist's role included dispensing medications, complying with regulations, advocating for quality therapeutic practices, and providing consultative services, research, and education. The perceived role of the veterinary pharmacist was viewed as being somewhat narrower. Compared to veterinary pharmacists, a more in-depth education in veterinary medicine was viewed as essential to the role development of veterinary pharmacy specialists. CONCLUSIONS: The authors hope their research will promote widespread awareness of the emerging field of veterinary pharmacy and encourage schools to offer increased access to clinically relevant professional training programs.