Veterinary medicine, development

The pharmaceutical industry has developed and studied a number of anabolic steroids for use in veterinary medicine and in rehabilitation from injuries that are accompanied by deterioration of muscles. The ideal agent would be one that possessed the anabolic properties of testosterone without its androgenic (masculinizing) effects. Methandrostenolone (Dianabol) and stanozolol are among the many synthetic anabolic steroids that require a prescription. 

A large and rapidly growing number of clinical trials (phase I and phase II) evaluating the potential of DNA vaccines to treat and prevent a variety of human diseases are currently being performed ( http // clinicaltrials.gov) however, there is yet no licensed DNA vaccine product available for use in humans. The clinical trials include the treatment of various types of cancers (e.g., melanoma, breast, renal, lymphoma, prostate, and pancreas) and also the prevention and therapy of infectious diseases (e.g., HIV/ABDS, malaria, Hepatitis B vims, Influenza vims, and Dengue vims). So far, no principally adverse effects have been reported from these trials. The main challenge for the development of DNA vaccines for use in humans is to improve the rather weak potency. DNA vaccines are already commercially available for veterinary medicine for prevention of West Nile Vims infections in horses and Infectious Hematopoetic Necrosis Vims in Salmon. 

The previous chapters examined the process for the development and authorisation of a drug product containing a ne v active ingredient for human use. This represents the most arduous path to market for any medicinal product. This chapter proceeds to examine the process of bringing a veterinary medicinal product to market. While the process shares most of the principles that apply to human drugs, there are some additional features that are unique to veterinary products. These include methods of use and the requirement to evaluate vithdra val periods and maximum residue limits in food-producing species. 

The process of developing and bringing to market veterinary medicines is fundamentally the same as that for human medicines. However, there are a number of features associated with veterinary medicines that can have either a positive or negative bearing on the overall process. 

A further aspect that may add to the development work relates to the method of administration. In addition to the standards methods of administration associated with human medicines, veterinary medicines may be introduced to animals through medicated feeds. Such practices have been most commonly associated with the use of antibiotics or other substances to enhance animal performance under intensive farming systems. The use of medicated feeds has been phased out in Europe since the end of 2005, with the exception of coccidiostats and histomonostats intended to kill or inhibit protozoa. In the U SA, however, medicated feeds are still commonplace. Thus, the developer may have to consider the stability and appropriate labelling of the drug when compounded into medicated feeds. 

As vith human pharmaceuticals, all safety studies must be conducted in accordance vdth the principles of Good Laboratory Practice (GLP). Similar to the International Conference on Harmonisation (ICH), the Veterinary International Conference on Harmonisation (VICH) has developed agreed guidelines on the types of test and other considerations that need to be addressed during the development and evaluation of veterinary medicines. A list ofVICH guideline topics is provided in Table 7.1. 

A unique feature of the development of veterinary medicines for food-producing species is the need to consider the establishment of Maximum Residue Limits (M RLs) for the drug or its metabolites in food produce. A MRL is defined in the European Union as ... 

Phencyclidine (l-[l-phenylcyclohexyl] piperidine, PCP) was originally developed as an intravenous anesthetic in the 1950s. Used for this indication, it causes a trance-like state without loss of consciousness and was hence classified as a dissociative anesthetic. However, it was soon withdrawn from human use because it produced unpleasant hallucinations, agitation, and delirium. The product was later used in veterinary medicine. Ketamine, a chemically closely related substance, was developed to replace PCP and is stiU in use as a dissociative anesthetic in children. Ketamine is less potent than PCP, and its effects are of shorter duration. However, it may also cause hallucinations (see the section on ketamine in Chapter 7, Club Drugs ). Much of the ketamine sold on the street (special K, cat Valium) has been diverted from veterinarians offices. 

This is a large subject that can only be dealt with in the barest outline in the present text. Many antibacterial and antifungal compounds have been discovered in microorganisms, and some of them have been successfully developed as antibiotics for use in human and veterinary medicine. They lie outside the scope of this book. A considerable number of other microbial compounds act as insecticides, acaricides, or herbicides, although few of them have been developed commercially (Copping and Menu 2000, Copping and Duke 2007). 

Development and Validation of a Proposed Regulatory Method, EMEA/CVMP/573100, Vol. 8, Veterinary Medicinal Products Establishment of Maximum Residue Limits (MRLs) for Residues of Veterinary Products in Foodstuffs of Animal Origin, Committee for Veterinary Medicinal Products, London (2001). Also available on the World Wide Web http //www.emea.eu.int/pdfs/vet/swp/057300en.pdf. 

The use of immunoassays for the determination of pesticides and veterinary medicines in food animals has increased since the early 1990s. The advantages of simple analysis, quick results, and high throughput make immunoassays a powerful technique for problematic matrices commonly encountered in animal agriculture. Careful development and validation are required to obtain accurate results, however. This review has demonstrated that most immunochemical techniques have been designed for use with milk samples, but a number of applications have also been developed for liver and muscle samples. The development of immunoassay techniques for residue analysis in eggs has clearly not been pursued to the extent of other edible tissues. 

Phencyclidine (PCP), one of the arylcyclohexylamines. was developed and originally used as a general anesthetic for humans. Due to psychotic and hallucinogenic reactions, use of the drug for humans was discontinued. It is now used legally only in veterinary medicine as an animal immobilizing agent. 

EMEA/CVMP/315/98 final Development pharmaceutics for veterinary medicinal products (August 1999)... 

A number of different adjuvant preparations have been developed (Table 13.13). Most preparations also display some associated toxicity and, as a general rule, the greater the product s adjuvanticity, the more toxic it is likely to be. A few different adjuvants may be used in veterinary medicine however (for safety reasons), aluminium-based products are the only adjuvants routinely used in human medicine. Application of many of the aggressive adjuvant materials is reserved for selected experimentation purposes in animals. 

Chloramphenicol (CAP) is a broad-spectrum antibiotic that was widely used in veterinary medicine. Since 1994 the use of CAP is banned in the EU because of certain toxicological problems (i.e., aplastic anemia and the grey baby syndrome ) observed in its administration to humans [ 107] that have prompted the establishment of a zero tolerance for the presence of these residues in meat and animal products. As a consequence, many efforts have been made to develop sensitive methodologies capable of detecting CAP residues or its metabolites. 

A series of 7-diazabicycloalkyl quinolones has been prepared and found to exhibit excellent broad spectrum activity against important veterinary pathogenic bacteria [105], The structures of several of these interesting bicyclic analogues (76) as well as MIC data are summarized in Table 6.28. Compound (76e) (danofloxacin), which also exhibits excellent p.o. and s.c. activity in a mouse protection model for Pasteurella multocida [ 106], is undergoing development for use in veterinary medicine. It has been shown to exhibit excellent bioavailability properties in cattle, swine and poultry [107] and is efficacious in models for the treatment of respiratory diseases in food-producing animals [108],... 

Substances used only for process-orientated research and development are exempt from registration for 5 years. The exemption can be extended for a further 5 years in exceptional circumstances, or 10 years for substances used exclusively to develop human or veterinary medicines. The manufacturer or importer has to inform the ECA of the substance identity, labelling and quantity, justify the quality, summarise the research programme and list the customers. 

Vaccination against viral and bacterial diseases has been one of the success stories of human and veterinary medicine. Probably the most outstanding example of the effectiveness of vaccination is the eradication of smallpox. In 1967 between 10 and 15 million cases of smallpox occurred annually in some 33 countries. By 1977 the last naturally occurring case was reported in Somalia. Polio, too, has been controlled in developed countries, for example the number of cases in the USA was reduced from over 40,000 per year in the early 1950s, before a vaccine was available, to only a handful of cases in the 1980s. Diphtheria is now almost unheard of yet over 45,000... 

A series of monoclonal antibodies were generated that can bind dimetridazole (269) and other nitroimidazole drugs used in veterinary medicine. An extraction procedure was developed for these nitroimidazoles that is compatible with a competition ELISA method, based on binding of these antibodies to the drugs. As little as 1 ng of 269 could be detected in turkey muscle by this method552. 

Toutain, P.L., Pharmacokinetic/pharmacodynamic integration in dmg development and dosage-regimen optimization for veterinary medicine, AAPS PharmSci., 4, 2002. 

Several perspective trends for development of the research concerning domestic animals cells hybridization and obtaining cell systems for biotechnology, human and veterinary medicine can be determined. They are creating hybrids with macrophages, hepatocytes, neurocytes, nucleated and... 

Many of the sulfur compounds are toxic but essential for life. The gas from elemental sulfur and from most of the compounds of sulfur is poisonous when inhaled and deadly when ingested. This is the reason that sulfur compounds are effective for rat and mice extermination as well an ingredient of insecticides. Sulfa drugs (sulfanilamide and sufadiazine), although toxic, were used as medical antibiotics during World War II before the development of penicillin. They are still used today in veterinary medicine. 

The future development of aminoglycosides for use in veterinary medicine will depend on two main factors. The first is the cost of producing them as the synthetic process is expensive. The second is depdendent on discovering an aminoglycoside that does not accumulate and remain in kidney tissue for prolonged periods, resulting in a shorter withdrawal period for food producing animals (11). 

Specialized antibiotic formulations have been developed for DCT, with physicochemical properties chosen to confer prolonged retention in the mammary secretions (21,, ). Ziv ( ) has summarized the desirable kinetic and other properties of such a product. The following antibiotic formulations are presently approved by the U.S. Center for Veterinary Medicine, FDA for infusion into the dry mammary gland erythromycin (300 mg), oxytetracycline-HCl (426 mg), benzathine cloxacillin (500 mg), cephapirin benzathine (300 mg), novobiocin (400 penicillin (200,000 lU) novobiocin (400 mg), penicil-... 

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