Pharmacokinetic profiles of the active metamizole metabolites in healthy horses

Metamizole (MT) is an analgesic and antipyretic drug labelled for use in humans, horses, cattle, swine and dogs. MT is rapidly hydrolysed to the active primary metabolite 4-methylaminoantipyrine (MAA). MAA is formed in much larger amounts compared with other minor metabolites. Among other secondary metabolites, 4-aminoantipyrine (AA) is also relatively active. The aim of this research was to evaluate the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.) and intramuscular (i.m.) routes in healthy horses. Six horses were randomly allocated to two equally sized treatment groups according to a 2 9 2 crossover study design. Blood was collected at predetermined times within 24 h, and plasma was analysed by a validated HPLC-UV method. No behavioural changes or alterations in health parameters were observed in the i.v. or i.m. groups of animals during or after (up to 7 days) drug administration. Plasma concentrations of MAA after i.v. and i.m. administrations of MT were detectable from 5 min to 10 h in all the horses. Plasma concentrations of AA were detectable in the same range of time, but in smaller amounts. Maximum concentration (Cmax), time to maximum concentration (Tmax) and AUMC0-last of MAA were statistically different between the i.v. and i.m. groups. The AUCIM/AUCIV ratio of MAA was 1.06. In contrast, AUC0-last of AA was statistically different between the groups (P < 0.05) with an AUCIM/AUCIV ratio of 0.54. This study suggested that the differences in the MAA and AA plasma concentrations found after i.m. and i.v. administrations of MT might have minor consequences on the pharmacodynamics of the drug

Hypertrophic osteopathy associated with a bronchial foreign body (grass awn) in a dog: a case report

A five-year-old dog was referred with a five-month history of lethargy, decreased appetite, cough and intermittent forelimb lameness. Radiographs revealed an intra-thoracic lesion and a marked periosteal bone apposition of the second digit on the left forelimb. As it was palisading and circumferential, the latter appeared typical of hypertrophic osteopathy (HO). A grass awn in a sub-lobar ramification of the right caudal bronchus was identified and removed by bronchoscopy. At three months follow-up, the digit appeared clinically normal. On radiographs the periosteal bone reaction had decreased, indicative of resolving hypertrophic osteopathy. Thoracic radiographs showed no abnormalities five months after foreign body removal and the bone lesion on the digit had disappeared. Successful treatment of the pulmonary foreign body abscess led to spontaneous regression of HO and eventually to complete resolution of clinical signs. To the authors’ knowledge, this is the first reported case of HO secondary to a bronchial-pulmonary grass an abscess

Pharmacokinetics of tramadol and its major metabolite after intramuscular administration in piglets

Tramadol (T) is a centrally acting atypical opioid used for treatment of dogs. Piglets might experience pain following castration, tooth clipping and tail docking and experimental procedures. The aim of this study was to assess the pharmacokinetics of T and its active metabolite M1 in male piglets after a single intramuscular injection. Six healthy male piglets were administered T (5 mg/kg) intramuscularly. Blood was sampled at scheduled time intervals and drug plasma concentrations evaluated by a validated HPLC method. T plasma concentration was quantitatively detectable from 0.083 to 8 h. M1 was quantified over a shorter time period (0.083–6 h) with a Tmax at 0.821 h. The study demonstrated that piglets produce a larger amount of M1 compared with dogs, horses and goats. The human minimum effective concentration of M1 (40 ng/mL) was exceeded for over 3 h in piglets. If it is assumed to also apply to piglets, it could be speculated that the drug efficacy might exert its action over 3 h or longer. This assumption has to be confirmed by further specific pharmacokinetic/pharmacodynamic studies

Pharmacokinetic Evaluations of Sulpiride After Intravenous, Intramuscular, and Oral Single-Dose Administration in Jennies (Equus asinus)

Sulpiride is an antipsychotic human drug. It is commonly used to encourage ovulation in noncycling mares and to stimulate lactation in adoptive mares. No pharmacokinetic data are available for donkeys. The aim of this study was to assess the pharmacokinetics profile of sulpiride after intravenous (IV), intramuscular (IM), and oral (PO) administrations in healthy jennies. Animals (n ¼ 6) were treated with sulpiride, 1 mg/kg by IV, IM, and PO routes according to a randomized cross-over design (3 3 Latin square). Blood samples (5 mL) were collected at predetermined times and analyzed using a validated high performance liquid chromatography with fluorescence detection method. IV and IM administrations gave similar curves, but they were not bioequivalent. The IM average bioavailability was 73.5%. After PO administration, the drug plasma concentrations were low and consequently both area under the curve and bioavailability (9.4%) were low. This finding could be because of the physicochemical features of the drug. Indeed, considering that sulpiride is a weak base, existing in the ionized form at gastric and physiological pH, it is unsurprising that it is poorly absorbable, especially in equine species whose gastric pH is particularly acidic. In conclusion, injective routes are definitely preferable to PO dosing because of the very low F% via this route

Hyperplastic and atrophic changes in the genital tract of a female cat following repeated treatment with deslorelin acetate – a case report

This study aimed to investigate the morphological patterns of the genital tract after long-term treatment of deslorelin acetate in a female cat, a gonadotropin-releasing hormone agonist currently used in adult cats to obtain transient oestrus suppression. A 1-year-old Chartreux female cat was treated with 4.7 mg deslorelin acetate to suppress oestrus manifestations. The treatment was repeated for a total of × 3 every 2 years. After 8 years, the female cat came into oestrus again, but she was no more implanted, and an ovariohysterectomy was performed. Before surgery, an ultrasound examination was performed that showed a normal uterus and the presence of about 5 follicles in ovaries. Concentrations of oestradiol, progesterone, and vaginal smears were compatible with oestrus. During surgery, a very short ovarian pedicle was observed yet neither uterus nor ovaries presented appreciable alterations. At histology, the ovaries presented a juvenile appearance with numerous primordial and periovulatory follicles. The uterus showed marked endometrial hyperplasia with polypoid projection and atrophic myometrium. Based on this case report, deslorelin acetate is a powerful drug able to preserve ovarian function. However, the suppression of gonadotrophin, especially for a long period, has a detrimental atrophic effect on the target organs during treatment and, on the opposite, hyperplastic changes may occur after the restoring of normal cyclicity

Guaiphenesin-ketamine-xylazine infusion to maintain anesthesia in mules undergoing field castration.

Abstract Background: In order to determine whether a combination of guaiphenesin, ketamine and xylazine can induce safe and satisfactory anaesthesia in mules undergoing field castration, eight healthy adult intact male mules were employed. They were premedicated with intravenous (IV) xylazine (1.3 mg/kg); an additional dose of xylazine (0.3 mg/ kg IV) was administered in case of inadequate depth of sedation. Anaesthesia was induced with IV thiopental (6 mg/ kg). The quality of sedation and induction was recorded. Anaesthesia was maintained with an infusion of guaiphenesin (50 mg/mL), ketamine (2 mg/mL) and xylazine (1 mg/mL) (GKX). The spermatic cord of each testis was infiltrated with 5 mL of 2% lidocaine. During anaesthesia heart rate (HR), respiratory rate (RR), rectal temperature (RT) and haemoglobin oxygen saturation ( SpO2) were measured every 5 min. The data were analysed with simple one-way analysis of variance (ANOVA). A P value < 0.05 was considered statistically significant. Time of anesthesia, time of surgery and time of recovery were recorded. Results: Only one mule required an additional dose of xylazine to achieve a satisfactory depth of sedation. Thiopental at the dose of 6 mg/kg IV resulted in smooth induction and lateral recumbency in all animals. GKX provided adequate anaesthesia to perform castration in all mules. Muscle relaxation was deemed adequate and physiological variables remained stable and within references values during the anaesthesia and did not change in response to surgical stimulation. Time (mean ± standard deviation) from the end of the infusion to sternal recumbency and time from sternal recumbency to standing were 27.7 ± 4.6 and 30.1 ± 7.7 min, respectively. Conclusions: The combination of xylazine, thiopental and GKX provides satisfactory short-term anaesthesia in mules undergoing field castration

Flupirtine: Preliminary Pharmacokinetics in the Donkey

Flupirtine (FLU) is a nonopioid analgesic drug with no antipyretic or antiphlogistic effects labeled for humans. It does not induce the side effects associated with the classical drugs used as pain relievers (Non steroidal antiinflammatory drugs and opioids) in human beings. The aim of this study was to evaluate the pharmacokinetic profiles of FLU after IV and PO administrations in healthy donkeys. Six Amiata breed adult jennies were randomly assigned to two treatment groups using an open, 2 × 2 Latin-square crossover study design. Group 1 (n = 3) received a single dose of 1 mg/kg of FLU injected IV into the jugular vein. Group 2 (n = 3) received FLU (5 mg/kg) via nasogastric tube. The washout period was 1 week. Blood samples (5 mL) were collected at 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, 36, and 48 hours, and plasma was then analyzed by a validated high-performance liquid chromatography method. No adverse effects were noticed in either administration group. After IV and PO administrations, FLU was detectable in plasma for up to 24 hours. The mean elimination half-life was longer after PO (10.81 hours) than after IV (0.90 hours) administration. The clearance was fast, and the area under the plasma concentration–time curve was small, findings consistent with a low PO bioavailability of about 20%. The pharmacokinetic trend of FLU in donkeys was different from those earlier reported in cats and dogs. Further studies are needed to understand if this active ingredient may be used in donkeys