Pharmacokinetic and pharmacodynamic modelling after subcutaneous, intravenous and buccal administration of a high-concentration formulation of buprenorphine in conscious cats

The aim of this study was to describe the joint pharmacokinetic-pharmacodynamic model and evaluate thermal antinociception of a high-concentration formulation of buprenorphine (Simbadol™) in cats

Face validity of a proposed tool for staging canine osteoarthritis: Canine OsteoArthritis Staging Tool (COAST)

Abstract Osteoarthritis (OA) is a common, progressive degenerative disease of synovial joints. It can develop subsequent to an acquired disorder such as joint trauma but is primarily driven by developmental orthopedic disease in young dogs. Therefore, it is essentially characterised as an early onset but lifelong disease that worsens with age. Early intervention using a multi-modal drug and non-drug approach, with or without surgery as required, has the greatest potential for the most effective management of the disease. Timely implementation of a continuing care plan provides an opportunity to slow the rate of deterioration by reducing the negative impacts of OA-associated pain, encouraging appropriate levels of activity and improving strength and posture. Unfortunately, many dogs are presented to veterinary clinics only when marked behavioural changes are observed and substantial deterioration of the musculoskeletal and somatosensory systems has already occurred. To assist veterinarians with early and stage-specific diagnosis of OA in dogs, the authors present a proposed, practical diagnostic aid called 'COAST' (Canine OsteoArthritis Staging Tool) with face validity. As indicated by the successful implementation of staging systems for other companion animal diseases, it is expected that standardized staging of OA in dogs will help guide disease management plans and improve monitoring. The items used to construct COAST have been developed using consensus opinion of international experts from nine countries, who are actively working in the fields of small animal orthopaedics, anaesthesia and pain management. Further validation (test-retest, discriminatory ability, responsiveness, criterion validation) of the tool under field conditions is now required and the authors invite input

An Update on Drugs Used for Lumbosacral Epidural Anesthesia and Analgesia in Dogs

This review aims to report an update on drugs administered into the epidural space for anesthesia and analgesia in dogs, describing their potential advantages and disadvantages in the clinical setting. Databases searched include Pubmed, Google scholar, and CAB abstracts. Benefits of administering local anesthetics, opioids, and alpha2 agonists into the epidural space include the use of lower doses of general anesthetics (anesthetic “sparing” effect), perioperative analgesia, and reduced side effects associated with systemic administration of drugs. However, the potential for cardiorespiratory compromise, neurotoxicity, and other adverse effects should be considered when using the epidural route of administration. When these variables are considered, the epidural technique is useful as a complementary method of anesthesia for preventive and postoperative analgesia and/or as part of a balanced anesthesia technique

Quality of amoxicillin/clavulanic acid oral formulations for intended veterinary use in the UK, Malaysia, Serbia and Thailand

© 2023 The Authors. Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.This is an open access article under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Objectives: Amoxicillin/clavulanate is the most commonly used oral antimicrobial drug in companion animals. The objective of the study was to detect types and frequency of deficits in the quality of veterinary oral formulations of amoxicillin/clavulanate in various countries. Materials and Methods: In a prospective study with purposive sampling, amoxicillin/clavulanate tablet formulations for canine use were collected in four countries (wholesalers or veterinary practice) and shipped to a central bioanalytical laboratory. Twenty‐four samples were collected from the UK (nine), Malaysia (nine), Serbia (four) and Thailand (two), yielding 18 different formulations (10 veterinary). Packaging inspection, tablet disintegration and content assay were conducted (validated high‐performance liquid chromatography with ultra‐violet detection); content was acceptable when within the 90% to 120% pre‐specified range (US Pharmacopeia). Results: Secondary packaging was present for 13 of 24 samples and primary packaging integrity was verified for all but one sample. Amoxicillin trihydrate/potassium clavulanate label ratio was 4:1, except for three formulations (2:1). Tablet dose strength ranged from 250 to 625 mg. All formulations contained both analytes. For amoxicillin, two of 24 samples were out of specification with 72.8% (Malaysia) and 82.3% (Thailand) of labelled content. For clavulanate, four of 24 samples were out of specification with 46.9% (Serbia), 79.0% (UK), 84.3% (Serbia) and 86.5% (Thailand) of labelled content. One formulation (Thailand) failed for both analytes. Clinical Significance: Antimicrobial formulations of substandard quality have negative consequences for efficacy in patients and potentially promote antimicrobial resistance. There was evidence of substandard formulations in all countries, not only for amoxicillin but especially for clavulanate; this could compromise equitable access to acceptable quality essential veterinary medicines worldwide.Peer reviewe

Ileal mucosal bile acid absorption is increased in Cftr knockout mice

BACKGROUND: Excessive loss of bile acids in stool has been reported in patients with cystic fibrosis. Some data suggest that a defect in mucosal bile acid transport may be the mechanism of bile acid malabsorption in these individuals. However, the molecular basis of this defect is unknown. This study examines the expression of the ileal bile acid transporter protein (IBAT) and rates of diffusional (sodium independent) and active (sodium dependent) uptake of the radiolabeled bile acid taurocholate in mice with targeted disruption of the cftr gene. METHODS: Wild-type, heterozygous cftr (+/-) and homozygous cftr (-/-) mice were studied. Five one-cm segments of terminal ileum were excised, everted and mounted onto thin stainless steel rods and incubated in buffer containing tracer (3)H-taurocholate. Simultaneously, adjacent segments of terminal ileum were taken and processed for immunohistochemistry and Western blots using an antibody against the IBAT protein. RESULTS: In all ileal segments, taurocholate uptake rates were fourfold higher in cftr (-/-) and two-fold higher in cftr (+/-) mice compared to wild-type mice. Passive uptake was not significantly higher in cftr (-/-) mice than in controls. IBAT protein was comparably increased. Immuno-staining revealed that the greatest increases occurred in the crypts of cftr (-/-) animals. CONCLUSIONS: In the ileum, IBAT protein densities and taurocholate uptake rates are elevated in cftr (-/-) mice > cftr (+/-) > wild-type mice. These findings indicate that bile acid malabsorption in cystic fibrosis is not caused by a decrease in IBAT activity at the brush border. Alternative mechanisms are proposed, such as impaired bile acid uptake caused by the thick mucus barrier in the distal small bowel, coupled with a direct negative regulatory role for cftr in IBAT function