LC-HRMS/MS study of the prodrug ciclesonide and its active metabolite desisobutyryl-ciclesonide in plasma after an inhalative administration to horses for doping control purposes.

Ciclesonide (CIC) is the first inhaled highly potent corticosteroid that does not cause any cortisol suppression. It has been developed for the treatment of asthma in human and more recently in equine. CIC is the active compound of Aservo® EquiHaler® (Boehringer Ingelheim Vetmedica GmbH), the pre-filled inhaler generating a medicated mist based on Soft Mist™ technology. This prodrug is rapidly converted to desisobutyryl-ciclesonide (des-CIC), the main pharmacologically active compound. Due to its anti-inflammatory properties, CIC is prohibited for use in horse competitions. To set up an appropriate control, the determination of detection times and screening limits are required. Therefore, a highly sensitive analytical method based on supported liquid extraction (SLE) combined with liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS) was developed to detect CIC and its active metabolite des-CIC in plasma. The lower limit of detection of CIC and des-CIC was approximately 1 pg/ml in plasma. After a pilot study conducted on a single horse at the recommended dose (eight actuations twice daily corresponding to 5.5 mg/day for the first 5 days, followed by 12 actuations once daily corresponding to 4.1 mg/day in the last 5 days), the same protocol was applied in the main study using six horses. In all horses, CIC and des-CIC levels were less than 5 and 10 pg/ml, respectively, at 36 h after the end of the administration. The outcome of this risk assessment study should be useful to draw any recommendations for horse competitions.

Dose range finding study for the efficacy of meloxicam administered prior to sodium urate-induced synovitis in cats.

OBJECTIVE: To determine the lowest efficacious dose of oral meloxicam for relieving pain in cats with a sodium urate (SU)-induced acute inflammatory synovitis. STUDY DESIGN: Randomized, blinded, controlled, and four-way crossover study. ANIMALS: Eight surgically neutered cats (four males, four females) paired according to sex. METHODS: Each pair of cats was treated with 0 (placebo), 0.025, 0.05, or 0.075 mg kg(-1) oral meloxicam once daily for 4 days prior to injection, into alternating stifles, of 1 mL of 20 mg mL(-1) SU crystals, beginning with the right stifle. Each cat received each of the four treatments, separated by at least 21 days. Analgesic efficacy was evaluated based on objective (e.g., pressure mat data total force, contact pressure, and contact area) and subjective (e.g., scores for Analgesia Scale [AS], Lameness Scale [LS], and Visual Analog Scale [VAS]) outcome measures for pain assessment. All outcome measures were recorded before and during 30 hours after SU injection. The pre-defined primary outcome measure was the area under the response-time curve (AUC(0-30) hours) of the total force of the injected limb. Data were analyzed by analysis of variance. A sequential test procedure was applied and the test sequence stopped in case of a nonsignificant result. RESULTS: Meloxicam at doses of 0.05 and 0.075 mg kg(-1) day(-1) PO was significantly different from placebo for the pre-defined primary outcome measure (i.e., AUC(0-30) hours of total force). All tested meloxicam doses were lower than placebo for the subjective outcome measures (i.e., AUC(0-30) hours of AS, LS, and VAS). CONCLUSIONS AND CLINICAL RELEVANCE: The lowest efficacious dose of meloxicam for relieving pain in cats with an SU-induced synovitis was 0.05 mg kg(-1) day(-1) PO according to the pre-defined primary outcome measure. However, lower doses may also be effective as seen in the subjective outcome measures.

Clinical evaluation of meloxicam versus ketoprofen in cats suffering from painful acute locomotor disorders.

The aim of this study was to evaluate the efficacy and palatability of meloxicam 0.5mg/ml oral suspension, compared to ketoprofen tablets in cats suffering from painful acute locomotor disorders. This single blinded, positively-controlled, randomised, multicentre trial involved 121 client owned cats. Cats received either meloxicam (0.5mg/ml oral suspension) at 0.1mg/kg on day 1 followed by 0.05mg/kg q 24h on days 2-5, or ketoprofen 5mg tablets at 1.0mg/kg q 24h for 5 days. The efficacy of the two treatments was assessed subjectively by clinicians on day 6 using a clinical sum score (CSS). Palatability and accuracy of dosing were also assessed. The baseline CSS was not significantly different between the groups, and after 5 days of treatment the CSS had decreased to a similar extent, reflecting a reduction in pain. There were no significant differences between the CSS of each group at day 6. Both treatments were well tolerated. Meloxicam was significantly more palatable than ketoprofen, and allowed for more accurate dosing. Meloxicam and ketoprofen are a safe and efficacious treatment for acute locomotor disorders in cats. Meloxicam (Metacam) may be associated with superior compliance in clinical practice due to the higher palatability, which results in better ease of administration.

Behavioural effects of ovariohysterectomy and oral administration of meloxicam in laboratory housed rabbits.

This study aimed to develop a behaviour-based pain assessment system for rabbits following ovariohysterectomy. Behaviour was analysed to assess the severity and duration of pain induced and determine the effects of administration of meloxicam. The results suggest that pain associated with ovariohysterectomy induced changes in the frequency and duration of a number of behaviours. The most indicative was inactive pain behaviour, which was observed very infrequently prior to surgery compared to very frequently immediately following surgery. This strongly suggests that this increase is a direct response to the surgical pain and/or stress. The frequency of inactive pain behaviour also decreased over the four days post-surgery suggesting that pain is decreasing during this time. High dose meloxicam (initial 1mg/kg followed 0.5mg/kg/day) induced some degree of analgesia. However, higher doses of meloxicam or in combination with an opioid may be required to provide consistent analgesia in rabbits following soft-tissue surgery.