Pharmacokinetic/pharmacodynamic modelling of robenacoxib in a feline tissue cage model of inflammation

Pelligand, L., King, J. N., Toutain, P. L., Elliott, J., Lees, P. Pharmacokinetic/pharmacodynamic modelling of robenacoxib in a feline tissue cage model of inflammation. J. vet. Pharmacol. Therap.  35 , 19–32. Robenacoxib is a novel nonsteroidal anti‐inflammatory drug developed for use in cats. It is a highly selective COX‐2 inhibitor. Results from previous feline studies showed that, despite a short half‐life in blood, the effect of robenacoxib persisted for 24 h in clinical studies. A tissue cage model of acute inflammation was used to determine robenacoxib’s pharmacokinetics and its ex vivo and in vivo selectivity for COX‐1 and COX‐2 using serum TxB₂ and exudate PGE₂ as surrogate markers for enzyme activity, respectively. After intravenous, subcutaneous and oral administration (2 mg/kg), the clearance of robenacoxib from blood was rapid (0.54–0.71 L·h/kg). The mean residence time (MRT) in blood was short (0.4, 1.9 and 3.3 h after intravenous, subcutaneous and oral administration, respectively), but in exudate MRT was approximately 24 h regardless of the route of administration. Robenacoxib inhibition of COX‐1 in blood was transient, occurring only at high concentrations, but inhibition of COX‐2 in exudate persisted to 24 h. The potency ratio (IC₅₀ COX‐1: IC₅₀ COX‐2) was 171:1, and slopes of the concentration–effect relationship were 1.36 and 1.12 for COX‐1 and COX‐2, respectively. These data highlight the enzymatic selectivity and inflamed tissue selectivity of robenacoxib and support the current recommendation of once‐daily administration.     

Hepatic tyrosine aminotransferase and glucocorticoid abuse in meat cattle

Bertarelli, D., Balbo, A., Carletti, M., Cannizzo, T., Girolami, F., Nebbia, C. Hepatic tyrosine aminotransferase and glucocorticoid abuse in meat cattle. J. vet. Pharmacol. Therap.  35 , 596–603. Besides being extensively applied as therapeutical remedies, glucocorticoids (GCs) – most notably dexamethasone or prednisolone – are also illegally used in livestock for growth‐promoting purposes. This study was designed to assess the suitability of liver tyrosine aminotransferase (TAT), a gluconeogenic enzyme known to be induced by GCs, to act as a reliable candidate biomarker to screen for GC abuse in cattle. Enzyme activity was measured spectrophotometrically in liver cytosols or in cell extracts, and TAT gene expression was determined by real‐time PCR. Compared with untreated veal calves, a notable scatter (20‐fold) and much higher median values (3‐fold) characterized TAT specific activity in liver samples from commercially farmed veal calves. A time‐related increase in both enzyme activity and gene expression was detected in rat hepatoma cell lines treated with dexamethasone concentrations (10^?8 or 10^?9 m ) in the range of those recorded in noncompliant samples from EU official controls. In experimental studies in which finishing bulls were administered GCs at growth‐promoting dosages, however, no such changes were recorded in dexamethasone‐treated animals; a statistically significant rise in liver TAT activity (+95%) only occurred in prednisolone‐treated bulls. Although further research is needed to characterize the GC‐mediated response in cattle liver, TAT does not appear to be a specific and sensitive biomarker of GC abuse in the bovine species.     

Successful reduction of a monozygotic equine twin pregnancy via transabdominal ultrasound‐guided cardiac puncture

In horses, twin pregnancy is pathological and represents a potentially life‐threatening condition to the mare and foal. Twinning occurs in approximately 2% of pregnancies. Of these, the majority of cases are dizygotic twins, resulting from 2 ovulations and monozygotic twins are rare. A 12‐year‐old Quarter Horse mare was presented for breeding management with shipped cooled semen and embryo transfer. Seven days post ovulation, a single late morula/early blastocyst was recovered and transferred immediately to a recipient mare. Thirty‐six days after transfer, transrectal ultrasound examination revealed the presence of 2 embryos. A transcutaneous reduction of one of the fetuses was performed successfully at 128 days of gestation. This report is the first to describe a successful reduction of monozygotic twins by transcutaneous ultrasound‐guided cardiac puncture.     

Reproductive Causes of Hypocalcemia

Reproductive causes of hypocalcemia include puerperal tetany (eclampsia) and mild hypocalcemia during whelping. This article reviews the pathophysiology, signalment, clinical signs, and treatment of eclampsia in the bitch and queen. The second part of the article focuses on the consequences and treatment of hypocalcemia prior to and during whelping in dogs and cats.