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Anand Agricultural University, Anand
Anand Agricultural University (AAU) was established in 2004 at Anand with the support of the Government of Gujarat, Act No.(Guj 5 of 2004) dated April 29, 2004. Caved out of the erstwhile Gujarat Agricultural University (GAU), the dream institution of Sardar Vallabhbhai Patel and Dr. K. M. Munshi, the AAU was set up to provide support to the farming community in three facets namely education, research and extension activities in Agriculture, Horticulture Engineering, product Processing and Home Science. At present there seven Colleges, seventeen Research Centers and six Extension Education Institute working in nine districts of Gujarat namely Ahmedabad, Anand, Dahod, Kheda, Panchmahal, Vadodara, Mahisagar, Botad and Chhotaudepur
AAU's activities have expanded to span newer commodity sectors such as soil health card, bio-diesel, medicinal plants apart from the mandatory ones like rice, maize, tobacco, vegetable crops, fruit crops, forage crops, animal breeding, nutrition and dairy products etc. the core of AAU's operating philosophy however, continues to create the partnership between the rural people and committed academic as the basic for sustainable rural development. In pursuing its various programmes AAU's overall mission is to promote sustainable growth and economic independence in rural society. AAU aims to do this through education, research and extension education. Thus, AAU works towards the empowerment of the farmers.
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ThesisItem Open Access STUDIES ON EFFECT OF KETOPROFEN AND FEBRILE CONDITION ON PHARMACOKINETICS OF LEVOFLOXACIN AND SAFETY OF LEVOFLOXACIN ALONE AND IN COMBINATION WITH KETOPROFEN IN SHEEP(AAU, Anand, 2009) PATEL, URVESHKUMAR DAHYABHAI; Thaker, A. M.Levofloxacin is a novel third generation fluoroquinolone with broad spectrum antibacterial activity. Use of non-steroidal anti-inflammatory drugs (NSAIDs) are frequently recommended with antibacterials for the treatment of various bacterial infections accompanied by fever and other inflammatory conditions in animals. Ketoprofen (KTP) is an aryl propionic acid derivative, non-selective COX inhibitor NSAID having anti-inflammatory, analgesic and antipyretic properties. In veterinary practice, ketoprofen is used to lower body temperature in animals having fever, to relieve bacteremia and pain in all animals. Pharmacokinetics of an antibacterial drug may change when administered with anti-inflammatory drug or in febrile animals. Despite the great potential for clinical use of levofloxacin, the data on its pharmacokinetics and safety profile in sheep are scarce. The present study was planned to determine the effect of intramuscularly administered ketoprofen (3 mg/kg) and febrile condition (lipopolysaccharide (LPS) induced) on pharmacokinetics of levofloxacin following intravenous, subcutaneous and oral administration (3 mg/kg) in sheep and safety of daily intravenous administration of levofloxacin alone (3 mg/kg) and in combination with intramuscular administration of ketoprofen (3 mg/kg) for five days in sheep by monitoring haematological and blood biochemical profiles.ThesisItem Open Access IMMUNOTOXICOLOGICAL STUDIES OF SUBACUTE ACEPHATE EXPOSURE IN WHITE LEGHORN COCKEREL BIRDS(AAU, Anand, 2006) TRIPATHI, SYAMANTAK MANI; THAKER, A. M.Acephate (Ace), a water-soluble insecticide, belongs to the phosphoramidothioate group of organophosphate (OP) insecticides. Acephate is an organophosphate foliar spray insecticide of moderate persistence with residual systemic activity of about 10-15 days. It is being widely used for the protection of vegetables and fruits due to its activity against lepidopterans and aphids. As this insecticide is in use as crop protectant, it is likely to cause indirect exposure in poultry through contamination of feed, soil and ground water (in very low amount) and hence, the present study was conducted in Day old White Leghorn Cockerels birds; approximate medium lethal dose (ALD50) of Acephate taken into consideration for the study was 852mg/kg. One hundred twenty five birds were divided into five different groups each comprising 25 birds. The birds of group Ci were given no treatment and served as control. Group C2 were administered groundnut oil (Iml/kg) and served as control (vehicle). Group T1 was put onl/40th of ALD50 (21.3 mg/kg), while group T2 received 1/30th of ALD50 (28.4 mg/kg) and group T3 was administered withl/20th of ALD50 (42.6 mg/kg) of Acephate suspended in 1 ml of groundnut oil. Once daily oral dosing was carried out for 28 days. All the birds were monitored for any observable toxic symptoms throughout the experimental period and they were also weighed weekly to monitor body weight gain. The blood samples were collected before sacrificing the birds on day 15 (after 14 days oral dosing) and day 29 (after 28 days oral dosing) of the study and were analyzed for hematological, biochemical and immunological parameters. Organ (liver, spleen, bursa and thymus) weights were recorded and organs (liver, spleen, bursa thymus, lung, and kidney) were collected for histopathological examinations. Severity and extent of the clinical signs varied according to dosage administered to the birds. The clinical symptoms observed were sudden onset of depression, reduced feed intake, dullness, ruffled feathers, cyanosis of comb, green diarrhea and severe limb weakness and some time paralysis. During the study period 6-8 birds died. Nervine symptoms like tremor, head down condition and torticolis were noticed only for few minutes before death. There was a reduction in the body weight of the Acephate treated birds. No alteration had been recorded in haematological parameters (hemoglobin, packed cell volume, total erythrocyte count and total leukocyte count) due to Acephate exposure. Dose dependent significant increase in blood glucose due to administration of Acephate was observed. A significant dose dependent increase in Serum Glutamic Oxaloacetate Transaminase and Serum Glutamic Pyruvate Transaminase and non significant increase in Lactate Dehydrogenase level of the birds treated with the Acephate indicates its systemic effect. A significant decrease in serum proteins during study was observed. A significant decrease in serum albumin and globulin were observed on 28th day of study. During the experimentation, Acephate had dose dependent immunosuppressive effect on Humoral immune response of birds from 28th day of experimentation. These findings indicate significant effect on protein metabolism and humoral immune response at the administered doses of Acephate. Cellular immunity was not affected as tested by DNCB dye test. Present study revealed that Acephate at administered doses seems to be toxic for multiple systems in growing WLH birds. Gross postmortem and histopathological changes in various organs of birds treated with Acephate were observed with typical organophosphate dose dependent toxicity signs. Microscopic changes observed in different organs viz. liver, lung, kidney spleen, thymus and bursa were of typical to organophosphate insecticide poisoning. Though, Acephate has been reported mild to moderately toxic to the birds; it seems that doses of Acephate given in the present study produce mild toxicity to multiple body systems of growing birds including immune system.ThesisItem Open Access TOXICOLOGICAL STUDIES OF SHROT TERM EXPOSURE OF BANTAMIZED WHITE LEGHORN BIRDS TO ACEPHATE(AAU, Anand, 2005) PATEL, NILENKUMAR P.; Thaker, A. M.The present study was conducted in 8 to 10 week old Bantamized White Leghorn birds; approximate medium lethal dose (ALD50) of Acephate use for the study was 852mg/kg. Ninety birds were divided into six different groups. The birds of group Ci was given no treatment and served as control. Group C2 was administered groundnut oil (1 ml/kg) and served as control (vehicle). Group T1 was given l/10th of ALD50 (85.2 mg/kg). Group T2 was put on 1/20th of ALD50 (42.6 mg/kg), while group T3 received 1/30th of ALD50 (28.4 mg/kg) and group T4 was administered with 1/40th of ALD50 (21.3 mg/kg) of Acephate suspended in 1 ml of groundnut oil. Once daily oral dosing was carried out for 28 days. All the birds were monitored for any observable toxic symptoms throughout the experimental period and they were also weighed weekly to monitor body weight gain. The blood samples were collected from wing vein at weekly interval and were analyzed for haematological and biochemical parameters. After 28 days of administration of Acephate birds were sacrificed and organs (lung, liver, spleen, heart, kidney, brain and testes) were collected for histopathological examinations. Severity and extent of the clinical signs varied according to dosage administered to the birds. The clinical symptoms observed were sudden onset of depression, reduced feed intake, dullness, ruffled feathers, cyanosis of comb, green diarrhea and severe limb weakness and some time paralysis. Mortality was observed from third week which was in dose dependent manner. Nervine symptoms like tremor, head down condition and torticolis were noticed only for few minutes before death. There was a reduction in the body weight of the insecticide treated birds. No alteration had been recorded in haematological parameters (hemoglobin, packed cell volume, total erythrocyte count and total leukocyte count) due to Acephate exposure. Dose dependent significant increase in blood glucose due to administration of Acephate was observed. A significant dose dependent increase in Serum Glutamic Oxaloacetic Transaminase and Serum Glutamic Pyruvate Transaminase level of the birds treated with the insecticide after 7 days of treatment indicates their systemic effect. Increase in the triglyceride was observed in treated birds. A significant decrease in serum proteins during study was recorded. Dose dependent increase in the alkaline phosphatase was observed. During the experimentation, Acephate at all the doses inhibited acetylcholinesterase indicating neurotoxicity due to administration of Acephate. Present study revealed that though Acephate is moderately toxic to the birds; it seems to be toxic for multiple systems in growing birds at given dosage. Gross postmortem and histopathological changes in various organs of birds treated with Acephate were observed with typical organophosphate dose dependent toxicity signs. Microscopic changes observed in different organs viz. lung, liver, spleen, heart, kidney, testis and brain which were typical to insecticide poisoning. Though Acephate has been reported moderately toxic to the birds at the doses administered in this study produce toxicity to multiple systems of growing birds used in the studyThesisItem Open Access Comparative Evaluation of Dexamethasone Induced CYP3A and CYP2H1 Gene Expression by Quantitative RT-PCR in Bantam, Bantamized White Leghorn and White Leghorn Chicks(AAU, Anand, 2004) KALIA, ANIL KUMAR; Sarvaiya, J. G.The present work was planned to study induction of CYP3A and CYP2HI genes by Reverse Transcriptase polymerase chain reaction (RT-PCR) and Quantitative RT-PCR in Bantam, Bantamized White Leghorn and White Legiiorn chicles. Total RNA was extracted from the liver tissue samples using Tri Reagent based method. The quantity of extracted RNA was assessed spectrophotometrically at 260/280nm, and it ranged from 1.7 to 2.0 OD suggesting good quantity of RNA extraction. The quality of extracted RNA was checked by 1% formaldehyde agarose gel electrophoresis and it showed bands at 28s, 18s and 5s rRNA subunits suggesting good integrity of RNA. First strand cDNA was synthesized using one step RT-PCR Kit. The PCR was performed and the product was subjected to agarose gel electrophoresis which yielded targeted amplification of 1107 bp, 1567 bp and 486 bp amplicon for CYP3A, CYP2HI and p-actin genes, respectively. β-actin (house keeping gene) was used as an internal control for normalization of CYP3A and CYP2H1 gene transcripts. Quantitative RT-PCR was done to quantify gene expression level of CYP3A and CYP2H1 genes. Four end points were selected for sample dropping at 26th, 31st 36rd and 41st cycles to perform Quantitative RT-PCR. The quantity of expressed genes was detected by Gene tool software using 1 kb DNA ladder having concentration of 7.1 ng/0.5 μl at 500 bp as reference. Relative expression ratio of CYP3A and CYP2H1 genes was calculated by Relative Expression Software Tool (REST), It was found that CYP3A is up regulated by a factor of 1.271 and 1.2 in Bantam and White Leghorn chicks, respectively and down regulated by a factor of 11.385 in Bantamized White Leghorn chicks. In Bantamized White Leghorn and White Leghorn chicks CYP2H1 gene was down regulated by factor 1.68 and 1.3 respectively, but up regulated by a factor of 1.126 in case of Bantam chicks. The PCR efficiency ranged from 1.4 to 1.9, 1.36 to 1.8 and 1.36 to 4.4 for CYP3A, CYP2H1 and P-actin genes, respectively in Bantam, Bantamized White leghorn and White Leghorn chicks.ThesisItem Open Access STUDIES ON EFFECT OF KETOPROFEN, FEBRILE CONDITION AND BIOENHANCER TRIKATU AND ITS CONSTITUENTS ON PHARMACOKINETICS OF LEVOFLOXACIN AND SAFETY OF LEVOFLOXACIN IN GOATS(AAU, Anand, 2012) PATEL, JATINKUMAR HARGOVINDDAS; Thaker, A. M.Levofloxacin is a novel third generation fluoroquinolone with broad spectrum antibacterial activity. Use of non-steroidal anti-inflammatory drugs (NSAIDs) are frequently recommended with antibacterials for the treatment of various bacterial infections accompanied by fever and other inflammatory conditions in animals. Ketoprofen (KTP) is an aryl propionic acid derivative, non-selective COX inhibitor NSAID having anti-inflammatory, analgesic and antipyretic properties. In veterinary practice, ketoprofen is used to lower body temperature in animals having fever, to relieve bacteremia and pain in all animals. Pharmacokinetics of an antibacterial drug may change when administered with anti-inflammatory drug or in febrile animals. Despite the great potential for clinical use of levofloxacin, the data on its pharmacokinetics and safety profile in goat are scarce. Ancient and recent scientific literature cited reference of bioenhancer like Trikatu (Piperine) application to increase bioavailability of drug and nutrients. Moreover, it is well known in ruminant animals that oral bioavailability of drug is low as compared to monogastric animals. Looking to this, present study was conceptualized to determine the effect of intramuscularly administered ketoprofen (3 mg/kg body weight) and febrile condition (lipopolysaccharide (LPS) induced) on pharmacokinetics of levofloxacin following intravenous, subcutaneous and oral administration (4 mg/kg body weight) in goats and safety of daily intravenous and subcutaneous administration of levofloxacin alone (4 mg/kg body weight) and in combination with intramuscular administration of ketoprofen (4 mg/kg body weight) for five days in goats by monitoring hematological and blood biochemical profiles. Moreover, effect of bioenhancer Trikatu and its constituents (Piperine equivalent to 20 mg/kg body weight) on pharmacokinetics of levofloxacin following oral administration (4 mg/kg body weight) in goats was evaluated. In addition to this bioenhancing effect methanolic extract of Trikatu (30 mg/kg body weight), Piper longum (30 mg/kg body weight), Piper nigrum (30 mg/kg body weight) and Zingiber officinale (30 mg/kg body weight) was evaluated following oral administration of levofloxacin (4 mg/kg body weight). The high performance liquid chromatography apparatus comprising quaternary gradient delivery pump, UV detector and reverse phase C18 column at room temperature. The mobile phase consisted of a mixture of 1% triethylamine in water and acetonitrile (85:15 v/v) adjusted to pH 3.0 with ortho-phosphoric acid and pumped into column at a flow rate of 1.5 mL/min at ambient temperature. The HPLC data integration was performed using software Clarity (Version 2.4.0.190). Following intravenous administration of levofloxacin in normal, ketoprofen treated, and febrile goats, the plasma drug concentration > 0.015 µg/ml was detected up to 18 h. Following intravenous administration of levofloxacin in ketoprofen-treated goats, no significant changes in pharmacokinetic parameters were observed compared to pharmacokinetic parameters of levofloxacin in normal goats. Following intravenous administration of ievofloxacin in febrile goats, values of AUC (13.48 ± 0.48 µg.h/mL) and AUMC (40.01 ± 2.66 µg.h2mL) were significantly higher and Vdarea (1.05 ± 0.04 L/kg) was significantly lower than the values obtained following levofloxacin administration in normal goats.ThesisItem Open Access SUB-ACUTE ORAL TOXICITY STUDY OF ATORVASTATIN ALONE AND IN COMBINATION WITH VERAPAMIL FOLLOWING REPEATED ADMINISTRATION IN HYPERLIPIDEMIC RATS(AAU, Anand, 2012) PATEL, JAYESHKUMAR BACHUBHAI; Thaker, A. M.Atorvastatin, a second-generation potent inhibitor of 3-Hydroxy 3- Methylglutaryl coenzyme A reductase is indicated for the treatment of dyslipidemia. The present study was conducted to evaluate the toxicity potential of Atorvastatin alone and in combination with Verapamil in hyperlipidemic rats. The study was conducted on 48 male Wistar rats dividing them in various groups having six rats in each group. Group I served as vehicle control and received 1.0 ml of 0.5% sodium bicarbonate solution orally for 28 days of dosing period. Group II served as hyperlipidemic control. Atorvastatin was given orally at dose rate of 0.5, 2.5 and 5.0 mg/kg body weight in poloxamer-407 induced hyperlipidemic rats of group III, IV and V respectively. Poloxamer-407 induced hyperlipidemic rats of group VI, VII and VIII received Atorvastatin at dose rate of 0.5, 2.5 and 5.0 mg/kg body weight respectively and additionally received Verapamil orally at dose rate of 10 mg/kg body weight. Animals were observed daily for clinical signs and mortality, if any. Body weight and feed consumption were recorded at weekly interval. On 29th of study, animals were subjected to blood collection; blood and serum sample were analyzed for haematological and biochemical parameters respectively. At the end of study period, animals were sacrificed and necropsy was performed; tissues (cerebrum, cerebellum, lung, liver, kidney, heart, aorta, spleen and muscle) were collected for histopathological studies. Hyperlipidemic rat model was developed by intra-peritoneal injection of poloxamer-407 at the dose rate of 500 mg/kg body weight on day prior to start of study and subsequently at every third day throughout the study period. In this dyslipidemic rat model serum concentration of triglycerides, total cholesterol and low density lipoprotein cholesterol level was increased by 15.1, 5.2 and 8.7 fold respectively; whereas high density lipoprotein cholesterol level was decreased by 1.5 fold as compared to vehicle control rats. Hjperlipidemic rats treated with Atorvastatin alone at 5.0 mg/kg body weight and in combination with Verapamil at 10 mg/kg body weight demonstrated hunched posture and piloerection along with dullness and sluggishness in the last week of experiment. Feed consumption was significantly reduced in hyperlipidemic rats treated with Atorvastatin at doses of 2.5 and 5.0 mg/kg body weight in combination with Verapamil at 10 mg/kg body weight in 3rd and 4th week of experiment. During 3rd and 4th week of study, there was also significant reduction in body weight gain of hyperlipidemic rats treated with Atorvastatin at doses of 2.5 and 5.0 mg/kg body weight in combination with Verapamil at 10 mg/kg body weight Significant neutrophilia, thrombocytopenia and lymphocytopenia have been observed in hyperlipidemic rats treated with Atorvastatin at 5.0 mg/kg body weight in combination with Verapamil at 10 mg/kg body weight. Atorvastatin alone at 2.5 and 5.0 mg/kg body weight and in combination with Verapamil at 10 mg/kg body weight produced significant hypotriglyceridemia in dyslipidemic rats. Atorvastatin alone at 5.0 mg/kg body weight and in combination with Verapamil at 10 mg/kg body weight; and Atorvastatin at 2.5 mg/kg body weight in combination with Verapamil at 10 mg/kg body weight produced significant hypocholesterolemia in dyslipidemic rats. Daily oral administration of Atorvastatin alone at 2.5 and 5.0 mg/kg body weight and in combination with Verapamil at 10 mg/kg body weight for 28 days produced significant reduction in low density lipoprotein cholesterol and significant rise in high density lipoprotein cholesterol in dyslipidemic rats. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin level were significantly increased in hyperlipidemic rats treated with Atorvastatin alone at 2.5 and 5.0 mg/kg body weight and in combination with Verapamil at 10 mg/kg body weight. Daily oral administration of Atorvastatin alone at 5.0 mg/kg body weight; at 2.5 and 5.0 mg/kg body weight in combination with Verapamil at 10 mg/kg body weight for 28 days caused significant rise in serum creatinine level in hyperlipidemic rats. Atorvastatin alone at 5.0 mg/kg body weight and in combination with Verapamil at 10 mg/kg body weight; and Atorvastatin at 2.5 mg/kg body weight in combination with Verapamil at 10 mg/kg body weight caused significant elevation in serum creatine kinase and lactate dehydrogenase level in hyperlipidemic rats. Rats of all treatment groups along with hyperlipidemic control group showed pale liver grossly. In poloxamer-407 induced hyperlipidemic rats, Atorvastatin alone at 5.0 mg/kg body weight and in combination with Verapamil at 10 mg/kg body weight showed noticeable muscle wasting condition Microscopically, fatty changes were observed in liver sections of hyperlipidemic control rats. Microscopic changes observed in liver were necrosis of hepatocytes, mild fatty changes and mild degeneration in hyperlipidemic rats treated with Atorvastatin alone at 2.5 mg/kg body weight and in combination with Verapamil at 10 mg/kg body weight. While hyperlipidemic rats treated with Atorvastatin alone at 5.0 mg/kg body weight and in combination with Verapamil at 10 mg/kg body weight revealed multifocal areas of necrosis, congestion in sections of liver; and bile duct proliferation was evident. Skeletal muscle showed loss of striations in myofibers, segmental muscle fiber necrosis, mild mononuclear cell infiltration and focal muscle fiber necrosis in hyperlipidemic rats treated with Atorvastatin alone at 5.0 mg/kg body weight and in combination with Verapamil at 10 mg/kg body weight; and Atorvastatin at 2.5 mg/kg body weight and in combination with Verapamil at 10 mg/kg body weight. Variable extent of degenerative lesions were observed in myocardium in hyperlipidemic rats treated with Atorvastatin alone at 5.0 mg/kg body weight and in combination with Verapamil at 10 mg/kg body weight; and Atorvastatin at 2.5 mg/kg body weight and in combination with Verapamil at 10 mg/kg body weight. Kidney sections showed varying extent of degenerative and necrotic lesion in renal tubules in hyperlipidemic rats treated with Atorvastatin alone at 5.0 mg/kg body weight and in combination with Verapamil at 10 mg/kg body weight. Based on serum profile as well as microscopic lesions, it was clearly observed that Atorvastatin in combination with Verapamil exhibited pronounced hepatotoxic, myotoxic and nephrotoxic potential.ThesisItem Open Access STUDIES ON EFFECT OF FEVER AND CO-ADMINISTRATION OF KETOPROFEN ON PHARMACOKINETICS OF MOXIFLOXACIN AND SAFETY OF SIMULTANEOUS ADMINISTRATION OF MOXIFLOXACIN AND KETOPROFEN IN SHEEP(AAU, Anand, 2012) SADARIYA, KAMLESH AMARSHIBHAI; Thaker, A. M.Moxifloxacin is a novel fourth generation fluoroquinolone with broad spectrum of antibacterial activity. The use of non-steroidal anti-inflammatory drugs (NS AIDs) is frequently recommended with antibacterials for the treatment of various bacterial infections accompanied by fever and other inflammatory conditions in animals. Ketoprofen (KTP) is an aryl propionic acid derivative, non-selective COX inhibitor NSAID having anti-inflammatory, analgesic and antipyretic properties. In veterinary practice, ketoprofen is used to lower body temperature in animals having fever, to reUeve bacteremia and pain in all animals. Pharmacokinetics of an antibacterial drug may change when administered with anti-inflammatory drug or in febrile animals. Despite the great potential for clinical use of moxifloxacin in India, the data on its pharmacokinetics and safety profile in sheep are scarce. Moxifloxacin was assayed in plasma by HPLC. The present study was planned to determine the effect of intramuscularly administered ketoprofen (3 mg/kg) and lipopolysaccharide (LPS) induced febrile condition on pharmacokinetics of moxifloxacin following intravenous and intramuscular administration (5 mg/kg) in sheep and safety of daily intramuscular administration of moxifloxacin (3 mg/kg) in combination with intramuscular administration of Icetoprofen (3 mg/kg) for five days in sheep by monitoring haematological and serum biochemical profiles. Following intravenous administration of moxifloxacin in normal healthy sheep, the plasma drug concentration > 0.17 ± 0.01 μg/ml was detected up to 12 h, while plasma drug concentration > 0.13 ±0.01 μg/ml was detected up to 18 h in ketoprofen treated and febrile sheep. The plasma drug concentrations in the present study were consistently higher in ketoprofen treated and febrile group than in normal sheep. Following intravenous administration of moxifloxacin in normal sheep, the mean distribution half-life (t1/2α), apparent volume of distribution (Vdarea), volume of distribution at steady-state (Vdss), area under plasma drug concentration-time curve (AUC0-∞), area under first moment curve (AUMC), elimination half-life (t1/2β), total body clearance (CIB) and mean residence time (MRT) were 3.55 ± 0.56 h, 4.88 ± 0.20 L/kg, 3.49 ± 0.11 L/kg, 8.38 ± 0.23 μg.h/mL, 49.52 ± 3.83 μg.h2/mL, 5.70 ± 0.37 h, 0.60 ± 0.02 L/h/kg and 5.87 + 0.32 h, respectively. Following intravenous administration of moxifloxacin in ketoprofen-treated sheep, the mean distribution half-life (t1/2α), apparent volume of distribution (Vdarea) and volume of distribution at steady-state (Vdss) were 2.63 ± 0.42 h, 1.67 ± 0.09 and 1.37 ± 0.02 L/kg, respectively. The elimination half-life (t1/2β), total body clearance (CIB) and mean residence time (MRT) were 4.08 ± 0.25 h, 0.29 ± 0.01 L/h/kg and 4.79 ± 0.07 h, respectively. The average values for area under plasma drug concentrationtime curve (AUC0-∞) and area under first moment curve (AUMC) were 17.55 ± 0.25 μg.h/mL and 84.14 + 1.96 μgh2/mL, respectively. Significant alterations in pharmacokinetic parameters in ketoprofen-treated and febrile sheep have been observed compared to normal sheep. Following intravenous administration of moxifloxacin in ketoprofen-treated sheep, a significant increase in mean value of various pharmacokinetic parameters like Cp0, A, B, p, AUC(0-∞) and AUMC were observed as compared to respective pharmacokinetic parameters of moxifloxacin in normal sheep. However, significant decrease in mean values of t1/2β, Vd(area), Vd(ss), C1(B) and MRT in ketoprofen treated group as compare to normal healthy sheep. In febrile sheep, the AUC (14.88 ± 0.39 μg.h/mL) and AUMC (88.82 ± 4.38 μg.h2/mL) were significantly (p<0.01) increased following intravenous administration of moxifloxacin. Significant (p<0.01) decrease in mean values of distribution half-life (t1/2α: 0.25 ± 0.03 h), total body clearance (CIB) (0.34 ± 0.01 L/h/kg), volume of distribution (Vdarea: 2.76 ± 0.04 L/kg) and volume of distribution at steady state (Vdss. 2.00 ± 0.03 L/kg) of the drug was observed in febrile compared to respective pharmacokinetic parameters in normal sheep.ThesisItem Open Access PHARMACOKINETIC INTERACTIONS OF TOLFENAMIC ACID AND MOXIFLOXACIN AND SAFETY OF TOLFENAMIC ACID IN WISTAR RATS(AAU, Anand, 2009) PATEL, SATISHKUMAR DAHYALAL; Thaker, A. M.Drug interactions may occur when two drugs are concurrently administered and one drug (or both) may influence the time course of the other in the body. Nonsteroidal anti-inflammatory drugs (NSAIDs) and antibacterial agents are prominent among the groups of drugs commonly prescribed together in veterinary medicine and they have enormous potential for drug interactions. Tolfenamic acid is a non-steroidal anti-inflammatory drug (NSAID) of the fenamate sub-group. Moxifloxacin is a novel fourth generation fluoroquinolone with broad spectrum antibacterial activity. The pharmacokinetic of tolfenamic acid (4.0 mg/kg) and moxifloxacin (5 mg/kg) as single drug and in combination after its intramuscular administration was investigated in male and female wistar rats. Tolfenamic acid and moxifloxacin were assayed in plasma by LC-MS/MS. Pharmacokinetic parameters were calculated by noncompartmental technique using computer software (WinNonlin, version 5.0.1). The present study also evaluated safety of tolfenamic acid (4 mg/kg) alone and in combination with moxifloxacin (5.0 mg/kg) after repeated administration at 24 h interval for 14 days in male and female wistar rats. The mean observed peak plasma concentration of tolfenamic acid following its administration as single drug and in combination with moxifloxacin in male rats were 4111.44 ± 493.15 and 3837.69 ± 351.83 ng/ml, where as in female rats mean values were 7114.74± 1409.96 and 7436.37±518.67 ng/ml, respectively, which was observed at 1 h respectively. The mean peak plasma concentration of moxifloxacin following its intramuscular administration as single drug and in combination with tolfenamic acid were 243.52 ± 13.66 and 397.62 ± 41.55 ng/ml, observed at 2 and 0.67 h, respectively in male rats, where as m female rats mean values were 200.74 ±28.67 and 255.88 ± 30.89 ng/ml, observed at 2 and 1 h, respectively. Following intramuscular administration of tolfenamic acid (4 mg/kg) as single drug and in combination with moxifloxacin (5 mg/kg) in male wistar rats the mean values of half-life (t 1/2), volume of distribution (Vz), clearance (CI) and area under plasma drug concentration-time curve (AUC (0-∞)) of tolfenamic acid were 2.59 ±0.16 and 3.27 ± 0.32 hr, 822.17 ± 115.38 and 1249.64 ± 139.52 ml, 218.39 ± 25.47 and 265.18 ± 11.36 ml/hr and 20280.77 ± 3501.67 and 15229.18 ± 678.80 hr.ng/ml, respectively. Whereas in female rats mean values of tolfenamic acid were 2.78 ± 0.39 and 2.66 ± 0.53 hr, 756.42 ± 166.09 and 559.68 ±76.19 ml, 179.76 ± 20.01 and 152.75 ± 10.34 ml/hr and 23524.07 ± 2324.79 and 26830.41 ± 1914.84 hr.ng/ml, respectively. Volume of distribution (Vz) was significantly higher in male rats following concurrent intramuscular administration of tolfenamic acid and moxifloxacin. Following intramuscular administration of moxifloxacin alone in male rats, the mean volume of distribution, half-life (t1/2), area under the plasma drug concentration time curve from 0.0 hr to infinity (AUC (0-∞)) and total clearance (CI) were 12679.07 ± 1121.74 ml, 2.52 ± 0.23 h, 1483.21 ± 184.65 hr.ng/ml and 3605.99 ± 394.29 ml/hr, respectively. Following intramuscular administration of moxifloxacin in combination with tolfenamic acid in male rats significant decrease in elimination half-life (ti/2: 1.69 ± 0.21 h) and volume of distribution (Vz: 7856.51 ± 495.60 ml) has been observed compared to moxitloxacin treatment alone. Following intramuscular administration of moxifloxacin (5 mg/kg) as single drug and in combination with tolfenamic acid (4 mg/kg) in female wistar rats the mean values of half-life (t1/2), volume of distribution (Vz), clearance (CI) and area under plasma drug concentration-time curve (AUC (0-∞)) of moxifloxacin were 1.98 ± 0.38 and 1.44 ± 0.21 hr, 15005.77 ± 2939.77 and 12488.86 ± 1708.16 ml, 5360.93 ± 502.91 and 6163.69 ± 563.64 ml/hr and 975.84 ± 93.57 and 851.60 ± 90.61 hr.ng/ml. respectively. There were non significant difference (p<0.05) in pharmacokinetic parameters of moxifloxacin in female rats following concurrent intramuscular administration with tolfenamic acid as compared to moxifloxacin. Repeated intramuscular administration of tolfenamic acid (4 mg/kg) alone and in combination with moxifloxacin (5 mg/kg) repeated at 24 h interval for 14 days in male and female wistar rats were found safe based on evaluation of haematological (Hb, RBC, WBC, MCV, MCH, MCHC, HCT and DLC), blood biochemical (AST, ALT, ALP, total bilirubin, total serum protein, serum albumin, globulin, serum creatinine, urea, uric acid and blood glucose) parameters. Moreover, no gross or microscopic changes were found in the liver, kidney, heart, spleen, stomach, intestine and joint cartilages of male and female wistar rats. The present study revealed that administration of tolfenamic acid and moxifloxacin together altered pharmacokinetic profile of each other. Therefore, concomitant use of both the drugs requires therapeutic monitoring for potential pharmacokinetic drug interaction.ThesisItem Open Access STUDIES ON PHARMACOKINETICS, BIOAVAILABILITY AND SAFETY OF KETOPROFEN IN SHEEP(AAU, Anand, 2008) GONDALIYA, SANJAY RAMESHBHAI; BHAVSAR, S. K.Levofloxacin is the active L - isomer of the racemate ofloxacin, a fluorinated quinolone has broad-spectrum activity and good antiKetoprofen is a non steroidal anti-inflammatory drug (NSAID) used for its antiinflammatory, analgesic and antipyretic properties in Veterinary medicine. The pharmacokinetics of ketoprofen after its single dose intravenous and intramuscular administration was investigated in six patanwadi breed of sheep by non compartmental approach. The drug was administered at the dose rate of 3.0 mg.kg-1 body weight and assayed in plasma by HPLC analysis. The present study also evaluated safety of ketoprofen (3.0 mg.kg-1) after repeated administration at 24 h interval for 5 days in sheep. Following intravenous and intramuscular administration of ketoprofen, values of elimination half-life (t1/2β), volume of distribution of drug at steady state [Vd(ss)], total body clearance (CIB), area under plasma drug concentration-time curve (AUC), and mean residence time (MRT) were 1.66 ± 0.12 and 3.31 ± 0.16 h; 0.31 ± 0.01 and 0.83 ± 0.08 L.kg-1; 5.53 ± 0.27 and 3.85 ± 0.30 ml.min-1.kg-1; 9.32 ± 0.32 and 13.58 ± 0.91 ng.h.ml-1 and 1.00 ± 0.06 and 3.67 ± 0.41 h, respectively. Following intramuscular administrationacterial activity at low plasma/tissue concentration. The present study was designed to investigate pharmacokinetics of levofloxacin following single dose intravenous and oral administration at the dose rate of 10 mg/kg of body weight and to evaluate safety after repeated administration (10 mg/kg) of levofloxacin at 12 hours interval for 14 days in layer birds. Drug concentration in serum was determined using High Performance Liquid Chromatography (HPLC). Following intravenous administration, the serum drug concentration-time curves were analyzed by non-compartmental approach. Following intravenous administration the therapeutically effective serum concentration of levofloxacm > 0.13 µg/ml was maintamed for up to 12 hours. Based on the serum drug concentrations, various pharmacokinetic parameters like elimination half-life (t1/2β) (3.08 ± 0.05 hours), apparent volume of distribution (Vd(area)) (4.02 ± 0.079 1/kg), volume of distribution of drug at steady-state (Vd(ss)) (3.23 ± 0.055 1/kg), total body clearance (CIB) (15.09 ± 0.21 ml/min/kg), area under serum drug concentration-time curve (AUG) (11.07 ± 0.14 µg.h/ml), area under first moment of curve (AUMC) (39.56 ± 0.89 µg.h2/ml) and mean residence time (MRT) (3.57 ± 0.052 hours) were determined. peak plasma concentration (Cmax) of 4.91 ± 0.52 was achieved at 0.5 h (tmax)- Bioavailability of the drug was 73.16 ± 5.58. Longer elimination half-life, larger volume of distribution at steady state and slower total body clearance of ketoprofen following intramuscular administration as compared to intravenous administration makes it more suitable for intramuscular use in sheep. Repeated intravenous administration of ketoprofen (3.0 mg.kg-1 body weight repeated at 24 h interval for 5 days) in sheep was found safe based on evaluation of haematological (Hb, PCV, TLC and DLC) and blood biochemical (AKP, ACP, AST, ALT, LDH, Total Bilirubin, Serum Creatinine, Total Serum Protein, Serum Albumin and Blood glucose) parameters except BUN. It is advisable to monitor kidney functions during long term therapy with ketoprofen in sheep. The present study indicate that intramuscular administration of ketoprofen at dose rate of 3.0 mg.kg'-1 in sheep would be provide a satisfactory plasma concentration of drug equal to its median effective concentration up to 18 h. Therefore, ketoprofen given via intramuscular route at the dose rate of 3.0 mg.kg-1 of body weight repeated every 18 h would be satisfactory therapeutic dosage regimen for sheep. However, therapeutic efficacy of the dosage remains to be evaluated in clinical cases under field conditions.