Carprofen in veterinary medicine. II. Inhibitory effect on the release of PGF2 alpha in the early postpartum cow

Carprofen, a non-steroidal anti-inflammatory drug (NSAID) known to inhibit prostaglandin synthesis, was given intravenously in five cows at a daily dose of 0.7 mg/kg for five days beginning on day 1 postpartum. Blood samples were collected at various times over a period of six days following the first injection. At this dose, carprofen reached highest plasma values of about 45 micrograms/ml after the fifth injection and was well tolerated by all the cows. During the whole experimental period, mean plasma levels of 15-keto-13, 14-dihydro-prostaglandin F2 alpha, the primary metabolite of PGF2 alpha, were significantly (p less than 0.05) lower in treated than in control animals (28-47% vs 64-101% of pretreatment concentrations). The suppressive effect of carprofen on PGF2 alpha-production occurred immediately after its application and was maximal 3-6 h post injection on the first and on the fifth experimental day (60-80% and 40-85%, respectively). We conclude from our results that carprofen in a single dose of 0.7 mg/kg b.w. effectively suppresses PGF2 alpha-release in the postpartum cow. Whether this effect is beneficial in the treatment of uterine inflammatory processes remains to be determined.     

The current epidemiological revolution in veterinary medicine. Part I

The nature of the current epidemiological revolution in veterinary medicine is considered in terms of the previous evolution of tactics for livestock disease management, and future prospects for epidemiological surveillance as the ‘core’ activity for public and private practice of preventive veterinary medicine.     

Some aspects of clinical pharmacokinetics in veterinary medicine. I

This series of two review articles deals with general aspects of the mechanisms which govern absorption and distribution of drugs within the body, and the kinetics of drug metabolism and excretion. Emphasis is given to the verification of pharmacokinetic principles in domestic animals, and the clinical applications which proceed therefrom. In the first part, the concept of the two compartment and three compartment models for drug disposition are introduced and developed to demonstrate the mathematical models which may be derived to describe the kinetics of drug distribution and elimination. In the second part bioavailability and drug dosage will be considered.     

Plasma disposition,faecal excretion and in vitro metabolism of oxibendazole following oral administration in horses

Oxibendazole (OBZ) was administered to eight horses at an oral dose of 10 mg kg(-1) bodyweight each. Parent OBZ could only be detected in plasma at the 0.5 and 1.0 hours post administration sampling times and the mean maximum plasma concentration was 0.008 microg ml(-1). Parent OBZ was detected in faeces between 12 and 72 hours after administration and the highest dry faecal concentration was detected at 24 hours. An unidentified metabolite was detected in plasma between 0.5 and 72 hours. The unidentified metabolite in the plasma of treated horses corresponded to the second eluted metabolite in the in vitro study. Metabolism of OBZ to its metabolite in vitro was significantly inhibited by co-incubation with the cytochrome P450 inhibitor piperonyl butoxide. These results indicated that first-pass metabolism decreases OBZ bioavailability in horses. The in vitro metabolism of OBZ was significantly inhibited by piperonyl butoxide and this could be utilised to extend the exposure of nematodes to the parent molecule.     

DNA diagnosis in veterinary medicine: I. DNA fingerprinting]

With the development of recombinant DNA-technology during the last 15 years, it became possible to analyse genetic variability directly at the level of genomic DNA. Restriction-Fragment-Length-Polymorphism (RFLP) and Highly-Variable-Regions (HVRs) lead to the development of new genetic markers, which can be used for the localization of normal and mutated genes. Some polymorphisms are hypervariable and can therefore be applied to carry out DNA-fingerprints thus identifying individuals from man and animals.     

Relation between milk urea content and nitrogen excretion from lactating cows

Abstract

Thirty-two Chinese Holstein lactating cows were used to investigate the relationship of milk urea nitrogen (MUN) and nitrogen excretion loading to the environment. Cows were fed a similar amount of forage, and concentrates according to milk production. Total collection of urine and faeces were conducted continuously for three days. The milk urea nitrogen was significantly correlated to total nitrogen excretion (R ²=0.70), urinary nitrogen excretion (R ²=0.85), and nitrogen excretion from faeces (R ²=0.22). The following equation was proposed to predict total nitrogen excretion (TNE) (g/d) based on milk urea nitrogen (MUN) (mg/dl): TNE?=?15.46(±1.83)×MUN?+?193.40(±28.79). The results obtained in this study suggested that MUN might be used to predict TNE from lactating cows.     

Plasma disposition and faecal excretion of oxfendazole, fenbendazole and albendazole following oral administration to donkeys

Fenbendazole (FBZ), oxfendazole (fenbendazole sulphoxide, FBZSO), and albendazole (ABZ) were administered orally to donkeys at 10mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment. The plasma and faecal samples were analysed by high performance liquid chromatography (HPLC). The parent molecule and its sulphoxide and sulphone (FBZSO(2)) metabolites did not reach detectable concentrations in any plasma samples following FBZ administration. ABZ was also not detected in any plasma samples, but its sulphoxide and sulphone metabolites were detected, demonstrating that ABZ was completely metabolised by first-pass mechanisms in donkeys. Maximum plasma concentrations (C(max)) of FBZSO (0.49microg/mL) and FBZSO(2) (0.60microg/mL) were detected at (t(max)) 5.67 and 8.00h, respectively, following administration of FBZSO. The area under the curve (AUC) of the sulphone metabolite (10.33microg h/mL) was significantly higher than that of the parent drug FBZSO (5.17microg h/mL). C(max) of albendazole sulphoxide (ABZSO) (0.08g/mL) and albendazole sulphone (ABZSO(2)) (0.04microg/mL) were obtained at 5.71 and 8.00h, respectively, following ABZ administration. The AUC of the sulphoxide metabolite (0.84microg h/mL) of ABZ was significantly higher than that of the sulphone metabolite (0.50microg h/mL). The highest dry-faecal concentrations of parent molecules were detected at 32, 34 and 30h for FBZSO, FBZ and ABZ, respectively. The sulphide metabolite was significantly higher than the parent molecule after FBZSO administration. The parent molecule was predominant in the faecal samples following FBZ administration. After ABZ administration, the parent molecule was significantly metabolised, probably by gastrointestinal microflora, to its sulphoxide metabolite (ABZSO) that showed a similar excretion profile to the parent molecule in the faecal samples. The AUC of the parent FBZ was significantly higher than that of FBZSO and ABZ in faeces. It is concluded that the plasma concentration of FBZSO was significantly higher than that of FBZ and ABZ. Although ABZ is not licensed for use in Equidae, its metabolites presented a greater plasma kinetic profile than FBZ which is licensed for use in horses. A higher metabolic capacity, first-pass effects and lower absorption of benzimidazoles in donkeys decrease bioavailability and efficacy compared to ruminants.     

Plasma concentration, mammary excretion and side-effects of phenylbutazone after repeated oral administration in healthy cows

Seven clinically healthy dairy cows were each given 2.5 gphenylbutazone (approximately 5 mg/kg body weight) by oral administration twice daily for 8 days. The concentrations of phenylbutazone in plasma and milk and several blood parameters were studied. The minium plasma concentration during steady state was 100.4 ± 7.3 μg/ml. During the same period the milk concentration never exceeded 1% of the plasma concentration. The elimination half-life in plasma was 38.6 ± 3.7 h. Five days after administration had been discontinued, the milk concentration was 0.05 ± 0.01 μg/ml. All seven cows were clinically healthy throughout the experiment. The most pronounced side-effect of the blood parameters studied was a decreased concentration of leucocytes to about two-thirds of the control value. This might have a pronounced influence on the effectiveness of the immune system. There was also a significant decrease in total bilirubin indicating a decrease in the breakdown of erythrocytes.     

Plasma kinetics,excretion in milk of eprinomectin,and its efficacy against Hypoderma spp. following topical administration in yaks

The plasma pharmacokinetics and mammary excretion of eprinomectin were determined in dairy yaks following topical administration at a dose of 0.5 mg/kg. The kinetics of plasma and milk concentrations were analyzed using a noncompartmental model. Plasma and milk concentrations of eprinomectin increased to reach maximal concentrations of 5.45 ± 2.84 and 2.29 ± 0.90 ng/mL at a T_max of 1.79 ± 0.57 and 2.00 ± 0.82 days, respectively. The concentration of eprinomectin in plasma was remained >0.5 ng/mL for more than 30 days after administration. The mean residence times of eprinomectin in plasma and milk were 14.73 ± 6.22 and 9.37 ± 2.81 days, respectively. The AUC value in plasma (55.89 ± 18.16 ng day/mL) was threefold greater than that in milk (18.02 ± 6.48 ng day/mL). The AUC milk/plasma ratio was 0.33 ± 0.08. The systemic availability of eprinomectin in yaks was lower than that observed value in other domestic bovines. The low level of eprinomectin excretion in milk suggests that eprinomectin can be used in yaks with zero milk‐withdrawal time. The efficacy of eprinomectin against naturally acquired larvae of Hypoderma spp. was also determined in yaks. Topically administrated eprinomectin at a dose of 0.5 mg/kg was 100% efficacious against larvae of Hypoderma bovis, H. lineatum, and H. sinense.     

Gene therapy in veterinary medicine.

Gene therapy in simple terms is the introduction of a gene into a cell, in vivo, in order to ameliorate a disease process. Human clinical trials have focused on the correction of monogenic deficiency diseases, cancer and AIDS. This paper summarises the technology of gene therapy, gives a brief synopsis of the current applications of gene therapy to veterinary medicine and discusses some of the problems which need to be overcome so that gene therapy can become accepted clinical practice.     

Ethical dilemmas in veterinary medicine.

Veterinarians frequently encounter situations that are morally charged and potentially difficult to manage. Situation involving euthanasia, end-of-life care, economics, and inadequate provision of care create practical and moral dilemmas. Ethical tension may be attributable to differences in beliefs regarding the moral value of animals, client and veterinary responsibilities, and deciding what is best for an animal. Veterinarians can employ communication skills used in medical situations to explore the reasons underpinning ethical dilemmas and to search for solutions with clients, staff, and colleagues.