Plasma concentrations of Tapentadol and clinical evaluations of a combination of Tapentadol plus Sevoflurane for surgical anaesthesia and analgesia in rabbits (Oryctolagus cuniculus) undergoing orchiectomy

Pain is probably under-treated in animals, particularly in rabbits, due to a lack of familiarity with the species and limited information about analgesic dose, efficacy and safety. Tapentadol (TAP) is a novel opioid drug, with a proven efficacy and safety profile in humans, which could be useful as an analgesic in rabbits. In a clinical study, TAP was administered (5 mg/kg, IV) to seven male New Zealand White rabbits 5 min before anaesthetic induction with sevoflurane to perform orchiectomy. Monitoring of vital signs, including heart rate, electrocardiogram, respiratory rate, invasive blood pressure, oxygen saturation, righting reflex, palpebral reflex, jaw tone and tongue retraction, was performed throughout surgery. Pain was assessed for 8 h following surgery, using previously validated parameters, physiological assessments and behavioural assessments. Blood was also collected at regular intervals to assess the pharmacokinetic profile of the drug. TAP was rapidly distributed and eliminated in rabbits. Apnoea did not occurred in any subject. Following surgery, there were very few observable signs of pain in four rabbits and all resumed normal activities within a few hours. In conclusion, this is the first study about the clinical effects and potential utility of TAP as an adjunct drug for anaesthesia and analgesia in the rabbit. However, further studies are still needed before its use in the veterinary clinical practice

Salmonella Vaccine Study in Oxford (SALVO) trial: protocol for an observer-participant blind randomised placebo-controlled trial of the iNTS-GMMA vaccine within a European cohort

Introduction Invasive non-typhoidal Salmonellosis (iNTS) is mainly caused by Salmonella enterica serovars Typhimurium and Enteritidis and is estimated to result in 77 500 deaths per year, disproportionately affecting children under 5 years of age in sub-Saharan Africa. Invasive non-typhoidal Salmonellae serovars are increasingly acquiring resistance to first-line antibiotics, thus an effective vaccine would be a valuable tool in reducing morbidity and mortality from infection. While NTS livestock vaccines are in wide use, no licensed vaccines exist for use in humans. Here, a first-in-human study of a novel vaccine (iNTS-GMMA) containing S. Typhimurium and S. Enteritidis Generalised Modules for Membrane Antigens (GMMA) outer membrane vesicles is presented. Method and analysis The Salmonella Vaccine Study in Oxford is a randomised placebo-controlled participant-observer blind phase I study of the iNTS-GMMA vaccine. Healthy adult volunteers will be randomised to receive three intramuscular injections of the iNTS-GMMA vaccine, containing equal quantities of S. Typhimurium and S. Enteritidis GMMA particles adsorbed on Alhydrogel, or an Alhydrogel placebo at 0, 2 and 6 months. Participants will be sequentially enrolled into three groups: group 1, 1:1 randomisation to low dose iNTS-GMMA vaccine or placebo; group 2, 1:1 randomisation to full dose iNTS-GMMA vaccine or placebo; group 3, 2:1 randomisation to full dose or lower dose (dependant on DSMC reviews of groups 1 and 2) iNTS-GMMA vaccine or placebo. The primary objective is safety and tolerability of the vaccine. The secondary objective is immunogenicity as measured by O-antigen based ELISA. Further exploratory objectives will characterise the expanded human immune profile. Ethics and dissemination Ethical approval for this study has been obtained from the South Central - Oxford A Research Ethics Committee (Ethics REF:22/SC/0059). Appropriate documentation and regulatory approvals have been acquired. Results will be disseminated via peer-reviewed articles and conferences. Trial registration number EudraCT Number: 2020-000510-14. © Authors 2023