Ketoprofen a safe and effective drug

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are commonly used in humans and animals for the treatment of mild to moderate pain in conditions like arthritis, osteoarthritis, ankylosing spondylitis and acute musculo-skeletal disorders. In 2006, a very popular and commonly used NSAID, diclofenac sodium was banned for veterinary use in Pakistan because of its reported toxicity in South Asian vultures. After the ban on diclofenac use in veterinary practice, search for newer and safer NSAlDs was made. We started the present research work at the department of pharmacology and toxicology, University of Veterinary and Animal sciences, (UVAS), Lahore, with the objective to find another effective and safe NSAID. For this purpose, toxicological screening and efficacy trials of different NSAIDs were carried out. The results of these experiments had indicated that the drug Ketoprofen is a safe and effective NSAID. Ketoprofen (KTP), is a powerful novel Non-Steroidal Anti Inflammatory Drug (NSAID), approved for human and veterinary use in more than 70 countries including Pakistan. After the ban on the use of diclofenac sodium in veterinary practice, Ketoprofen has become a popular anti pyretic, analgesic and anti inflammatory drug. Ketoprofen has wide therapeutic index, wider safety margin, lower toxicity potential and less incidence of adverse events than Aspirin, Phenylbutazone and Flunixin Meglumine. Favourable pharmacokinetic profile of Ketoprofen in humans, made it a suitable and effective NSAID for veterinary use. The efficacy and toxicity of drugs depends on the biological processes of absorption, distribution, metabolism and excretion (ADME). Pharmacokinetics is the discipline dealing with ADME. Its parameters are very useful for making recommendations regarding appropriate dosage and rational use of drug. The genetics and environmental factors affecting ADME, are responsible for inter individual, inter ethnic and inter species variations to clinical response to any drug therapy. Several reported studies have shown that inter species variations exist in clinical response to Ketoprofen. The pharmacokinetic profile of Ketoprofen in domestic animals specifically in our local buffaloes, goats, horses and dogs has not been studied yet in Pakistan. A research project duly approved by the university competent authorities was started in November 2009, at the department of Pharmacology and Toxicology, Uvas, Lahore. The main objectives of this research project were to develop, standardize and validate, a simple, specific and accurate High Performance Liquid Chromatography (HPLC) method, for the quantification of concentration of Ketoprofen in plasma, characterization of pharmacokinetic parameters of Ketoprofen in domestic animals, specifically in buffaloes, goats, horses, and dogs under local conditions, and evaluation of interaction effect of amoxicillin trihydrate on the pharmacokinetic parameters of Ketoprofen when Amoxicillin Trihydrate and Ketoprofen were co-administered in buffaloes. The study was completed in three phases. A simple, specific and accurate HPLC analytical method for the determination of Ketoprofen in plasma was developed, standardized and validated in phase-1 which was then used for the measurement of Ketoprofen in plasma of target animals in phase-II and phase-III. The characterization of pharmacokinetic parameters of Ketoprofen in buffaloes, goats, horses and dogs was made in phase-II. Where as interaction effect of Amoxicillin Trihydrate on the pharmacokinetic parameters of Ketoprof en, when both amoxicillin Trihydrate and Ketoprofen were co-administered in buffaloes was evaluated in phase-III. In phase-II, eight clinically healthy adult animals of each specie of buffaloes, goats, horses and dogs were arranged, tagged and acclimatized to the experimentation environment. Feed I Food and water was provided as per standard requirement. A qualified veterinary doctor monitored the health status of experimental animals throughout the research project. Animals were administered a single W dose of 3 mg/kg.B. Wt of Ketoprofen through jugular vein. Blood samples (3-5ml) were collected in vacutainers before and after medication at various time intervals starting from 0.08 hrs up to 96 hrs. Plasma was separated out and analyzed with already developed, standardized and validated HPLC method. The concentration of Ketoprofen in plasma was measured. In phase-III, eight clinically healthy adult buffaloes which were previously used in phase-II, were taken. A wash out period of 14 days was given to the buffaloes. After a wash out period, buffaloes were administered an 11M dose of amoxicillin Trihydrate @15mg/kg. B. Wt into the neck muscles and after 10 minutes, an W dose of 3mg/kg.B. Wt of Ketoprofen was given. Blood samples(3-5m1) were collected in vacutainers before and after medication at various time intervals starting from 0.08 hrs up to 96 hrs. Plasma was separated out and analyzed with already developed, standardized and validated HPLC method. The concentration of Ketoprofen in plasma was measured. The Pharrnacokinetic parameters were calculated by computer based Pharrnacokinetic soft ware APO version 3.02. The statistical analysis was done by using computer softwares SPSS.13. The comparison was made with non paired t test. The results of present study indicated that individual and species variations existed in the pharmacokinetic behavior of ketoprofen among buffaloes, goats, horses and dogs. No significant interaction effect of amoxicillin trihydrate on the pharrnacokinetic parameters of ketoprofen was observed. The pharrnacokinetic data of ketoprofen in one specie can not be extrapolated to another species. A J/V dose of 3 mg/kg.B. Wt is recommended in buffaloes and dogs in clinical conditions related to inflammation and dose can be repeated after 24 hours. A J/V dose of 3 mg/kg.B. Wt is recommended in horses and goats and dose can be repeated after 12 hours. Dose of ketoprofen can be same in different animals but different dosage regimens are required for different animals. It is suggested that there is a need to conduct clinical trials for assessment of minimum effective plasma concentration of ketoprofen in target animals in order to get its benefits as an analgesic and anti inflammatory agent. The interaction effect of ketoprofen with other antibiotics must be studied as ketoprofen is usually co-administered as an adjuvant and supportive to antibiotics against different infections. The government of Pakistan must direct manufacturers to mention species specific dosage regimens on the product inserts and labels of finished drugs instead of mentioning a generalized dosage regime.

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