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ThesisItem Open Access EFFECT OF PIPERINE ON THE PHARMACOKINETICS OF ENROFLOXACIN IN BROILER CHICKENS(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517502. (A.P.) INDIA, 2018-11) NAGARJUNA, NALLAPANENI; DILIP REDDY, G(MAJOR); RAVI KUMAR, P; SATHEESH, KThe study was aimed to evaluate the effect of piperine on the pharmacokinetics of enrofloxacin. It was aimed to study the effect of piperine co-administration and pre-treatment on the pharmacokinetics of enrofloxacin in broiler chickens(Vencobb). Adult birds weighing around 2.0 kg were randomly assigned to their equal groups with 10 birds in each. The treatment protocol consisted of single oral dose of enrofloxacin (10 mg/kg b.wt) (group 1), single oral dose of piperine (15 mg/kg b.wt) followed by single oral dose of enrofloxacin (10 mg/kg b.wt) (group 2) and piperine (15 mg/kg b.wt) orally for ten days followed by enrofloxacin (10 mg/kg b.wt) on the 10th day (group 3). Blood samples were collected from either left (or) right tarsal vein at 0 (blank), 0.166, 0.33, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 36 and 48 h post dosing and plasma was separated for HPLC analysis. The plasma concentration-time data were analysed by non-compartmental pharmacokinetic analysis. There was no significant (p>0.05) difference in Cmax among the three groups. Elimination rate constant (β) observed in group 3 birds (0.044±0.0031/h) was significantly (p<0.05) lower when compared to group 1 (0.061±0.001 1/h) and 2 birds (0.066±0.001 1/h), which reflected the elimination half-life, t1/2 in group 3 (16.130±0.898 h), where significantly (p<0.05) higher value was observed when compared to groups 1 (11.437±0.248 h) and 2 (10.510±0.155 h). Tmax recorded in group 2 birds (7.600±0.267 h) was significantly (p<0.05) higher than that of group 1 (4.550±0.462 h). AUCs (AUC0-t and AUC0-∞) recorded in group 3 (56.551±2.035 µg/ml.h and 66.382±2.973 µg/ml.h) were significantly (p<0.05) high; implying more amount of drug was present for longer time in the body. The AUCs (AUC0-t and AUC0-∞) observed in group 2 (44.073±1.357 µg/ml.h and 46.294±1.457 µg/ml.h) were comparatively higher than group 1 (36.268±3.501 µg/ml.h and 38.104±3.637 µg/ml.h), indicating the effect of piperine in increasing the absorption over period of time. The area under first moment curve (AUMC) and mean resident time (MRT) recorded in group 3 (1711.716±140.298 µg/ml.h2 and 25.379±1.212 h) were significantly (p<0.05) higher than those recorded in groups 1 (654.193±65.964 µg/ml.h2 and 17.077±0.364 h) and 2 (808.749±38.688 µg/ml.h2 and 17.391±0.384 h). The increased values indicate that high concentration of enrofloxacin was present in the circulation for longer time in piperine pre-treated birds. The clearance observed in group 3 (0.154±0.008 L/kg/h) was significantly (p<0.05) lower when compared to group 2 (0.218±0.007 L/kg/h) and further the clearance of group 2 was significantly (p<0.05) lower than that of group 1 (0.282±0.024 L/kg/h). It can be concluded from the study that enrofloxacin administered after pre- treatment with piperine has exhibited higher t1/2, AUC, AUMC, MRT values and lower clearance values. The increase in plasma concentration of enrofloxacin in birds pre-treated with piperine could be attributed to the ability of piperine to enhance the intestinal absorption, to inhibit the metabolism in liver and to inhibit P-glycoprotein mediated drug efflux of during intestinal absorption. The increased AUC and half-life and decreased elimination rate constant could be helpful in designing formulations, that can be used in the treatment of resistant infections.ThesisItem Open Access ROLE OF EUGENOL IN REVERSAL OF VASCULAR DYSFUNCTION INDUCED BY EXPERIMENTAL DIABETES AND HYPERTENSION(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517502. (A.P.) INDIA, 2018-10) Vamsikrishna, Bobba; Srinivasa Rao, G(MAJOR); Ravi Kumar, P; Rama Devi, V; Vinoo, RABSTRACT : Phenylpropanoids are a diverse group of phytochemicals with immense health benefits and found throughout the plant kingdom. Eugenol is a member of the phenylpropanoids and is remarkably versatile molecule which is present abundantly in clove, nutmeg, cinnamon, basil and bay leaf. Epidemiological evidence and clinical trial data indicates that due to presence of biologically active phytochemicals, the plant originated diets can reduce the risk of chronic disease conditions such as cardiovascular disease, hypertension, diabetes and cancer. Hypertension and diabetes are the lifestyle diseases which are considered to be main causes of mortality for decades in humans. Vascular dysfunction is the major change that is associated with diabetes and hypertension. It is well documented that both diabetes and hypertension occur together in most of the human beings that is an additive cause for increase in risk of vascular complications. Though there are standard treatments available at present for these complications, a look for an alternative approach that can better address the vascular problems is most wanted. Hence the present study was designed to know the effect of eugenol against vascular dysfunction associated with either diabetes or hypertension alone and diabetes with hypertension together. The study was carried out in rats that are divided into eight groups with ten rats in each. Group-I (normal control) received vehicle alone for eight weeks whereas group II (eugenol control) received eugenol orally and daily at the rate of 80 mg/kg for eight weeks. Group- III, IV and V constitute experimentally induced hypertension control, diabetic control and diabetic rats with hypertension. Hypertension was induced in rats with administration of L-NAME in drinking water (40 mg/kg/day). Whereas single dose of streptozotocin was injected intraperitoneally at 40 mg/kg for inducing diabetes in rats. Group V rats received both streptozotocin and L-NAME. Group- VI (eugenol treated hypertensive rats), VII (eugenol treated diabetic rats) and VIII (eugenol treated diabetic rats with hypertension) received eugenol 80 mg/kg orally from the day after the onset of diabetes, hypertension or both conditions experimentally. Development of hypertension and diabetes in rats was confirmed by decrease in total nitrate/nitrite levels in serum and high blood glucose levels (>300 mg/dl) respectively. At the end of the study, rats were sacrificed and thoracic aorta was collected for studying vascular reactivity and histopathology. In addition, effect of eugenol in ameliorating the oxidative stress induced by experimental diabetes, hypertension and diabetes associated hypertension was also studied. Moreover, liver and kidney function markers in plasma were estimated in different study groups to know the effect of eugenol on liver and kidney function. Total nitrate (NO3-) and nitrite (NO2-) levels in serum were significantly (P < 0.05) decreased in hypertension control, diabetic control and diabetes associated hypertensive rats. Eugenol treatment had no impact on reversing the nitrate and nitrite levels in diabetes and hypertension back to the normal values noticed in control rats. Hyperglycemia was observed both in diabetic and diabetic hypertensive rats. Eugenol treatment did not have any effect in restoring the blood glucose levels to normal. Eugenol treatment could not show any favorable effect on body weight that had reduced in diabetic and diabetic hypertensive rats. Eugenol treatment had no effect on increased oxidative stress noticed in diabetic, hypertensive and diabetic hypertensive rats. Levels of liver function markers were raised in diabetic and diabetic hypertensive rats indicating liver damage and eugenol had no protective effect on liver damage. But elevated plasma creatinine, blood urea nitrogen levels and reduced plasma total protein in diabetic and diabetic hypertensive rats were restored to normal by eugenol treatment indicating protective effect of eugenol on kidney. Vascular reactivity was studied in-vitro by taking myographic recordings of aorta as described here; 1. Contractile response to phenylephrine and 5-HT. 2. Ach relaxation on phenylephrine and 5-HT induced contraction. 3. Eugenol relaxation of phenylephrine and 5-HT induced contraction. The lower mean log EC50 values of phenylephrine (-7.856 M) and 5-HT (-6.967 M) in hypertensive control and diabetic hypertensive rats (Phe: -7.960 M and 5-HT: -7.035 M) demonstrates hyper responsiveness of aortic smooth muscle to phenylephrine and 5-HT in comparison with normal control (Phe: -6.588 M and 5-HT: -5.700 M), and hyper-responsiveness of aorta to phenylephrine was partially reversed by eugenol treatment. But aorta from diabetic control rats showed hyper-responsiveness to phenylephrine (-7.137 M) and hypo reactivity to 5-HT (-5.247 M) compared to normal control rats. Eugenol treatment showed no impact on hyper-reactivity to phenylephrine or hypo-reactivity to 5-HT in diabetic rats. Maximum relaxation (% Emax) by acetylcholine in aorta on phenylephrine and 5-HT induced contractions was significantly reduced in diabetic, hypertensive and diabetic hypertensive rats. The effect was complete in hypertension and diabetic hypertension. Eugenol treatment had no significant change on acetylcholine induced relaxation in diabetic rats but significantly (P<0.001) improved relaxation in hypertensive and diabetic hypertensive rats. Eugenol produced dose dependent relaxation on phenylephrine and 5-HT induced contraction in all experimental groups but its effect was less potent than acetylcholine. Emax of eugenol on phenylephrine induced contraction was reduced in hypertensive, diabetic and diabetic hypertensive rats. Eugenol treatment to diabetic and diabetic hypertensive rats significantly improved Emax of eugenol. Eugenol relaxation on 5-HT induced contraction in diabetic control, hypertensive control and diabetic hypertensive rats were similar to control rats. The pathological changes observed in aorta, heart and kidney due to hypertension, diabetes and diabetic hypertension were not reestablished to normal with eugenol treatment. In conclusion, eugenol partially reversed phenylephrine and 5-HT induced vascular hyper-responsiveness in aorta and augmented the relaxation to acetylcholine in hypertensive and diabetic hypertensive rats but failed to produce a similar response in diabetic rats. However, eugenol had no role in maintaining blood glucose and serum nitrate levels indicating its inability to alleviate diabetes and hypertension. Further, eugenol treatment could not modulate oxidative stress and histopathological changes induced by diabetes and hypertension in plasma, heart and kidney. Further studies are needed to know the molecular mechanism involved in partial reversal of vascular dysfunction by eugenol.ThesisItem Open Access ENDOCRINE DISRUPTING ACTIONS OF CADMIUM AND EXPERIMENTAL EVALUATION OF PROTECTION BY GREEN TEA EXTRACT(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2014-05) SHIVAKUMAR, PABBATHI; GOPALA REDDY, A(MAJOR); SRINIVASA RAO, G; ANJANEYULU, Y; RAMANA REDDY, Y; UDAYA KUMAR, MABSTRACT : An experimental study was conducted to evaluate the neuro-endocrine disrupting actions of cadmium and the effect of cadmium on the progeny that were born to cadmium exposed rats and to evaluate the protective role of green tea on neuro-endocrine disrupting actions of cadmium in Sprague dawley rats. Rats were randomly divided into 4 groups of 30 rats in each (male rats =12, female rats=18).Group 1 served as Sham control Group 2 treated with CdCl2, Group 3 treated with Green tea extract treatment and Group 4 Cd + green tea extract treatment. Blood was collected from all the groups at monthly intervals for analyzing sero-biochemistry (blood glucose, total cholesterol, HDL-cholesterol, triglycerides, total protein and albumin, biomarkers of cardiovascular, hepatic and renal pathology, and hormonal profile (thyroid profile, sex hormones). The key enzymes concerned with metabolism were assayed. Immune status was studied at the end of 3rd month by phytohaemagglutinin assay. Rats were subjected to neuro-behavioural studies at the end (Elevated plus maze and Morris water maze). Epididymal sperm count in males and estrous cycle pattern in females were studied. At the end of 3 months, 12 rats (6 males and 6 females) from each group were sacrificed to collect various organs and endocrine glands and subjected them to biochemical, histological and electron microscopic studies. Cadmium concentration was estimated in all the treated groups in kidney, testes, liver and brain at the end of 3 months. In all the groups, twelve (12) females were mated at the end of three months with male rats belonging to respective groups/treatments and the treatment was continued till 17th day of gestation. 50% of the pregnant rats in the respective groups were sacrificed on day 19 to study skeletal and soft tissue developmental anomalies and the rest were allowed to normal delivery. The pups of F1 generation from all the groups were kept till weaning (post-natal day 21) and were subjected to sero biochemical, neurobehavioural studies andthyroid hormone profile were estimated. There were significant alterations in sero-biochemistry biomarkers of cardiovascular, hepatic and renal pathology and hormonal profile thyroid profile, group 2 as compared to group 1.Treatment group revealed significant improvement in all the parameters as compared to group 2, while the combination treatment group 4 was found better The histological studies in group 2 revealed marked changes in all the organs studied, while groups 4 revealed moderate changes and groups 1 and 3 revealed no pathologically significant changes. The electron microscopy of kidney, testis and thyroid revealed marked alterations in architecture in group 2, while groups 4 revealed better architecture. There were no significant alteration in the TEM samples of the offspring and there were no skeletal abnormalities in the offspring as evidenced by skeletal staining. The results of the study revealed neuro-endocrine disrupting actions of cadmium and protctive role of green tea in cadmium toxicity. Further studies are warranted to know in detail on the endocrine disrupting actions of cadmium and protective role of green tea at various concentrations.ThesisItem Open Access SYNTHESIS AND EVALUATION OF ANTIBACTERIAL ACTIVITY OF ENROFLOXACIN CONJUGATED NANO ZINC OXIDE(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2018-05) Mulla Hussain Basha; Bharavi, K(MAJOR); Srinivasa Rao, G; Annapurna, PABSTRACT : Antimicrobial resistance is a major concern in veterinary medicine. In this study, the successful conjugation of enrofloxacin with amine functionalized zinc oxide nanoparticles (ZNP) was described and its antibacterial activity was evaluated against standard MTCC cultures and clinical isolates. ZNP were synthesized using microwave-assisted method using zinc acetate dihydrate. 3-aminopropyltriethoxysilane (3-APTES) was used to amine functionalize ZNP using co-condensation technique. Enrofloxacin was conjugated with amine functionalized ZNP using 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). ZNP, enrofloxacin and enrofloxacin conjugated zinc oxide nanoparticles (ECZN) the conjugate were analyzed by using various techniques like UV-Vis spectrophotometery, Dynamic light scattering (DLS),Transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FTIR) analysis to assess the nano size and conjugation. The antibacterial activity of ECZN was evaluated using microtitre dilution method using standard MTCC cultures (S.aureus - MTCC 3160, S.pyogenes - MTCC 1927, S.typhimurium -MTCC 3224, E.faecalis - MTCC 9845, E.coli - MTCC 443, P.aeruginosa -MTCC 3542 and K.pneumoniae - MTCC 432) and clinical isolates (E.coli, Salmonella sps, and S. aureus). ZNP were spherical with uniform distribution and a diameter of 20 nm. The particles showed a characteristic peak at 380 nm with a hydrodynamic radius of 28.3 nm, zeta potential of -29.7 mV. The FTIR spectra of ZNP exhibited characteristic peaks at 3398.57 (3400) cm−1, 1553.79 (1632) cm−1. Successful amine functionalization of ZNP was confirmed by the observation of deep purple colour in ninhydrin test. The FTIR spectra of amine functionalized ZNP shows a characteristic peak at 3307.29 cm−1 (due to the presence of O–H and –N–H stretching of NH2 group); 2967.24 cm−1 (due to the asymmetric C–H stretching of the CH2 group of APTES); 1626.18 cm−1 and 1461.78 cm−1 (due to NH2 scissoring of primary amine). The conjugation of enrofloxacin with amine functionalized ZNP (efficacy: 1.18 mg%) was confirmed by UV-Vis spectra and FTIR Native enrofloxacin exhibited two characteristic peaks at 280 nm and 321 nm. After conjugation with ZNP, the second peak slightly shifted to 375 nm while the first peak remained the same. In the FTIR spectra ECZN showed peaks obtained in the region of 1400–1550 cm−1 which were similar to enrofloxacin peaks, while 896.47 cm−1 signified Zn– O stretching. The MIC (μg mL-1) of enrofloxacin was significantly (P<0.05) reduced against respective MTCC culture in combination with ZNP (enrofloxacin in native form vs enrofloxacin in ECZN) (S.aureus – 0.106 vs 0.0637*; S.pyogenes – 0.065 vs 0.0245*; S.typhimurium – 0.032 vs 0.0051*; E.faecalis – 0.021 vs 0.0083*; E.coli – 0.047 vs 0.0187*; P.aeruginosa – 2.611 vs 0.1444*; K.pneumoniae – 0.0.65 vs 0.0944*). Against clinical isolates, the MIC of native vs ECZN (actual enrofloxacin concentration) were comparable (E.coli – 0.0975 vs 0.083; Salmonella sps – 0.079 vs 0.069; S.auerus – 0.111 vs 0.086). However, the MIC of ECZN against both standard cultures and clinical isolates was significantly (P<0.05) lower than ZNP. In conclusion, enrofloxacin could be successfully conjugated with amine functionalized zinc oxide nanoparticles. The antibacterial efficacy of ZNP was improved in the combination with enrofloxacin against standard MTCC cultures and clinical isolates. In future, ways to improve the efficacy of enrofloxacin conjugation with zinc oxide nanoparticles and spectrum of activity could be explored.ThesisItem Open Access ANTICARCINOGENIC ACTIVITY OF CINNAMALDEHYDE AND NANO CINNAMALDEHYDE AGAINST MAMMARY CANCER IN RATS(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2018-05) Ravi, Killi; Ravi Kumar, P(MAJOR); Bharavi, K; Rama Devi, V; VINOO, RABSTRACT: Cancer is a growing health problem in both developing and developed countries. Cancer chemoprevention is defined as the use of natural or synthetic agents that reverse, suppress or arrest carcinogenic and/or malignant phenotypic progression towards invasive cancer. The effectiveness of many anticancer drugs is limited due to their inability to reach the target site in sufficient concentrations and efficiently exert the pharmacological effect on affected cells without harming the healthy cells. Therefore, the search for new anticancer agents with better efficacy and fewer side effects is an ongoing phenomenon. Plant phenolic compounds are a group of secondary metabolites with wide pharmacological activities (Al-Rimawi et al., 2016). Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of different oxidative associated diseases such as cancer (Dai and Mumper, 2010). trans- Cinnamaldehyde is a phenolic compound found naturally in various species of the genus Cinnamomum and is used in preparing beverages, medicinal products, perfumes and cosmetics. Nanoparticles (NPs) are versatile agents with a variety of biomedical applications including drug delivery. Keeping this in view, the present study was undertaken to evaluate the anticancer potential of cinnamaldehyde (CNMA) and its nano preparation, the nano zinc cinnamaldehyde (CZN) in chemical induced rat breast cancer model. Further, cinnamaldehyde was also studied for its disposition kinetics in rats. For induction of mammary tumors, fifty days old virgin female Sprague-Dawley rats were administered with single oral dose of 20 mg dimethyl benz(a)anthracene (DMBA). Those rats positive for mammary tumors on 90th day were only selected for further studies. The study was carried out in seven experimental groups viz. normal control (C), DMBA control (DMBA-C), cinnamaldehyde prophylactic (CNMA-P), cinnamaldehyde treatment (CNMA-T), nano cinnamaldehyde control (CZN-C), nano cinnamaldehyde treatment (CZN-T) and tamoxifen (TAM). CNMA-P group rats received cinnamaldehyde (50 mg/kg b.wt) orally starting from the 45th day i.e. five days prior to the DMBA administration and continued to received the same until the end of the study on 120th day. CNMA-T, CZN-C and TAM treatment groups received the respective treatments for a period of 30 days beginning from the 90th day. All the animals were sacrificed on 120th day. Plasma concentration of cinnamaldehyde and cinnamic acid were estimated in rats administered with cinnamaldehyde at a dose rate of 500 mg/kg b.wt. From the pharmacokinetic study it was evident that cinnamaldehyde is rapidly converted into cinnamic acid (CA). Apparent volume of distribution (Vd) and plasma clearance (Cl) were high for CNMA but its AUC0-t, MRT and t1/2 values were low when compared to CA. Tumor volume, tumor multiplicity, tumor burden, body weight, tissue antioxidant and peroxidation status and various plasma biochemical parameters including total sialic acid (TSA) levels were assessed in all experimental groups. In addition tumor latency period was recorded in CNMA-P group. Mammary tumor tissues were subjected to light and electron microscopic examination for pathological changes and immunohistological studies for the presence of estrogen and progesterone receptors. Prophylactic treatment with cinnamaldehyde increased the tumor latency period and decreased the tumor volume, tumor burden and tumor multiplicity. Compared to DMBA control group, cinnamaldehyde and its nano preparation showed favourable results in terms of tissue antioxidant profiles and plasma biochemical parameters. Mild to moderate regressive changes were observed in various treatment groups. However tamoxifen treated rats showed greater extent of favourable changes in terms of tumor histology. The study revealed that, cinnamaldehyde (CNMA) and nano zinc cinnamaldehyde (CZN) have mild degree of anticancer effects, with CZN being little more effective than CNMA. However CNMA was more effective when used prophylactically than when used as a therapeutic agent. Hence, it is likely that CNMA can reduce the possibility of breast cancer occurrence and severity when used prophylactically.ThesisItem Open Access PHARMACOKINETIC STUDIES ON BETAINE IN BROILER CHICKENS INFECTED WITH COCCIDIA(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2018-04) USHA, N; Ravi Kumar, P(MAJOR); SRINIVASA RAO, G; Rama Devi, VABSTRACT: Betaine is a commercially used anti coccidial agent in poultry. Present study was aimed to know the pharmacokinetics of betaine hydrochloride in healthy and coccidia infected birds. Three week old birds were divided into three groups of five birds each. Group I and II consisted of normal healthy birds, while group III birds were experimentally infected with coccidia before the commencement of study. Group II and III birds received betaine hydrochloride @ 100 mg.kg-1 orally once, while group I birds received dextrose normal saline (DNS). Blood samples were collected from all the birds at pre determined time intervals to know the plasma concentration of betaine and to calculate various pharmacokinetic parameters using PKSolver, version.2.0. Betaine concentration ranged from 0.298±0.017 to 0.504±0.0115 mg.ml-1 and these represent the endogenous betaine levels. In group II healthy birds that received betaine hydrochloride once orally, plasma betaine concentration ranged from 0.455±0.041 to 1.186±0.204 mg.ml-1, while in group III coccidia infected birds it ranged from 0.435±0.088 to 1.233±0.264 mg.ml-1. The analysis of plasma concentration versus time data revealed that the AUC0-t and AUMC0-t values in healthy and coccidia infected birds were 11.138±1.54 mg.mL-1*h and 66.60±8.26 mg.mL-1*h2 while in coccidia infected birds they were 8.653±0.91 mg.mL-1*h and 45.49±4.54 mg.mL-1*h2 with non-significant difference. However MRT, t1/2 were found significantly decreased in coccidia infected birds (5.28±0.165 h; 3.66±0.11 h) compared to those observed in healthy birds (6.06±0.14 h; 4.20±0.101 h). The ß was observed to be significantly increased in coccidia infected birds (0.190±0.006 h-1) compared to that of healthy birds (0.16±0.003 h-1). The study further revealed increased Vdss (0.65±0.082 L.kg-1) and ClB (0.122±0.014 L.kg-1h-1) value in coccidia infected birds compared to healthy birds (0.636±0.13 L.kg-1; 0.102±0.01 L.kg-1h-1). The study revealed that presence of coccidial infection significantly altered the pharmacokinetics of orally administered betaine in poultry.ThesisItem Open Access PHARMACOKINETICS OF ALBENDAZOLE ADMINISTERED ORALLY ALONG WITH QUERCETIN AS CHITOSAN-ALGINATE ENCAPSULATED MICROSPHERES IN BROILERS(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2017-12) BHADRAIAH, A; DILIP REDDY, G(MAJOR); RAVI KUMAR, P; RAMA DEVI, VABSTRACT: The present study was aimed to investigate the pharmacokinetics of albendazole administered orally along with quercetin as chitosan-alginate encapsulated microspheres in broilers. Thirty two adult broilers were divided into four groups with eight birds in each group and the treatment was given as follows: groups I and II received pure albendazole orally and intravenously @ 10 mg/kg respectively, while groups III and IV received albendazole @ 10 mg/kg in modified formulations of chitosan-alginate and chitosan-alginate with quercetin respectively. Blood was collected at various time intervals. Plasma was separated by centrifuging the blood and was subjected to HPLC assay for estimation of albendazole and albendazole sulphoxide. The pharmacokinetic parameters were analyzed by non-compartmental model. In group I that received pure albendazole orally ABZ could not be detected in the plasma at any point of time, while in other three groups ABZ was detectable up to 9-12 h after administration. The Cmax of ABZ in groups II and IV was significantly higher when compared to group III, while tmax was significantly higher in group IV when compared to groups II and III. The AUC observed in group IV was significantly (~2.5 fold) higher compared to groups II and III. The volume of distribution and clearance of ABZ in group IV was significantly lower when compared to groups II and III. Albendazole sulphoxide, the active metabolite of albendazole, could be detected from one hour to 48 h in group IV compared to 0.5 to 36 h in group I, 0.083 to 36 h in group II and 0.5 to 48 h in group III. The pharmacokinetics of ABZ-SO revealed a significantly higher t1/2 and maximum Cmax in groups III and IV when compared to group I. The AUC observed in group II, III and IV was significantly higher compared to group I though the AUC observed in group IV was non-significantly lower than that of group III. The MRT observed in group IV was longer than that observed in groups I and II. Similar to its parent compound ABZ-SO also showed similar trend with respect to Vd and clearance. The results in present study indicate that the quercetin has increased the absorption of ABZ and decreased its metabolite formation probably by inhibiting intestinal/hepatic CYPs. The modified formulations containing chitosan-alginate and quercetin prolonged the absorption and elimination of the active metabolite of ABZ-SO as evidenced by increased Cmax, AUC, and MRT observed in groups III and IV. Keeping in view of the enhanced absorption of albendazole and improved relative bioavailability of its active metabolite albendazole sulphoxide from microsphere formulations containing chitosan and quercetin, further appropriate studies can be performed to identify their efficacy in combatting systemic helminthic infections.ThesisItem Open Access EFFECT OF LICORICE EXTRACT ON THE PHARMACOKINETICS OF MELOXICAM AND NIMESULIDE IN CHICKEN(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2017-10) SENTHILNATHAN, M; BHARAVI, K(MAJOR); SRINIVASA RAO, G; RAMA DEVI, VABSTRACT: The present study was aimed to investigate the pharmacokinetic interaction between meloxicam and nimesulide (which are NSAIDs and CYP2C9 substrates) and licorice, a CYP2C9 inhibiting flavonoid, in chicken. 32 chickens were divided into 4 groups with 8 birds in each group and the treatment was given as follows: Group I received meloxicam alone at the rate of 2mg.Kg-1 B.W orally; Group II received meloxicam at the rate of 2 mg.Kg-1 B.W orally 60 min after the pretreatment with licorice at the rate of 500 mg.Kg-1 B.W; Group III received nimesulide alone at the rate of 2 mg.Kg-1 B.W orally; Group IV received nimesulide at the rate of 2 mg.Kg-1 B.W orally 60 min after the pretreatment with licorice at the rate of 500 mg.Kg-1. Blood was collected by venipuncture at 0, 0.166, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h. Plasma was separated by centrifuging the blood and was subjected to HPLC assay for estimation of meloxicam and nimesulide. Pharmacokinetic parameters were calculated by non-compartmental technique. In group I, no pretreatment was carried out before the single oral bolus administration of meloxicam (2mg.Kg-1), meloxicam was detected up to 24 h, with the Cmax 3.44±0.50 μg.mL-1 at 6.50±0.47 h. The important pharmacokinetic parameters of meloxicam after single oral bolus administration were β: 0.14±0.03 h-1; t1/2β: 4.97±0.93 h; AUC0-∞: 68.35±13.20 μg.h.mL-1; AUMC0-∞: 1978.83±892.76 μg.h2.mL-1; Vdss: 0.54±0.10 L.kg-1; Clβ: 0.06±0.01 L.kg-1.h-1 and MRT: 9.24±0.95 h. Licorice (500mg.Kg-1, oral) was given 60 min before administration of meloxicam (2mg.Kg-1, oral) as pretreatment to in group II. The mean value of Cmax obtained was 4.26±0.55 μg.mL-1, which was not significantly high from the group I. The important pharmacokinetic parameters of meloxicam obtained were β: 0.19±0.03 h-1; t1/2β: 4.43±0.99 h; AUC0-∞: 49.09±9.20 μg.h.mL-1; AUMC0-∞: 608.69±213.28 μg.h2.mL-1; Vdss: 0.48±0.06 L.kg-1; ClB: 0.05±0.01 L.kg-1.h-1 and MRT: 9.50±0.54 h. Upon licorice pretreatment prior to meloxicam administration pharmacokinetic parameters such as AUC0-∞, ClB, t1/2β, Vdss and MRT were not increased significantly from the control group I. In group III, no pretreatment was carried out before the single oral bolus administration of nimesulide (2mg.Kg-1), nimesulide was detectable upto 12 h, with the Cmax 0.75±0.09 μg.mL-1 at 1.41±0.16 h. The important pharmacokinetic parameters of meloxicam after single oral bolus administration were β: 0.16±0.03 h-1; t1/2β: 5.43±1.23 h; AUC0-∞: 3.06±0.59 μg.h.mL-1; AUMC0-∞: 11.41±3.43 μg.h2.mL-1; Vdss: 2.47±0.38 L.kg-1; ClB: 0.88±0.19 L.kg-1.h-1 and MRT: 3.25±0.44 h. Licorice (500mg.Kg-1, oral) was given 60 min before administration of nimesulide (2mg.Kg-1, oral) as pretreatment to in group IV. The mean value of Cmax obtained was 0.75±0.15 μg.mL-1, which was not significantly differing from the group III. The important pharmacokinetic parameters of nimesulide obtained were β: 0.12±0.03 h-1; t1/2β: 7.82±1.69 h; AUC0-∞: 3.78±1.00 μg.h.mL-1; AUMC0-∞: 27.21±17.02 μg.h2.mL-1; Vdss: 2.76±0.51 L.kg- 1; ClB: 0.74±0.14 L.kg-1.h-1 and MRT: 4.09±0.63 h. Upon licorice pretreatment prior to nimesulide administration pharmacokinetic parameters such as AUC0-∞, ClB, t1/2β, Vdss and MRT were not increased significantly from the control group III.ThesisItem Open Access BIO-AVAILABILITY AND BIO-EQUIVALENCE OF ENROFLOXACIN CONJUGATED NANO ZINC OXIDE IN BROILERS(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2017-06) SRIRAMULU, L; BHARAVI, K(MAJOR); RAVI KUMAR, P; ANNAPURNA, PABSTRACT : Bioavailability and bioequivalence of enrofloxacin conjugated zinc oxide nano particles (ECZNP) in broilers was investigated in the present study. Forty adult broilers weighing approximately 2 kg were randomly divided into four groups consisting 10 birds in each group. Birds in group-I received ECZNP 10 mg.kg-1 by oral route, group-II received ECZNP 10 mg.kg-1 by intravenous route (IV), whereas group-III received standard enroflaxacin 10mg.kg-1 by oral route. Group-IV received standard enrofloxacin 10 mg.kg-1 by IV. Feed and water were withdrawn (12 hrs and 2 hrs respectively) before drug administration. Blood samples were obtained through both left and right jugular veins at predetermined time intervals i.e. for IV route at 0.83333 h, 0.166667 h, 0.25 h, 0.5 h, 0.75 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h and 48 h and for oral route at 0 h, 0.25 h, 0.5 h, 0.75 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 36 h and 48 h time intervals after administration of drugs. Plasma was separated by centrifuging at 2500 RPM for 15 min and stored at -20º C until analysed for ECZNP and enrofloxacin by microbiological assay using Escherichia coli (MTCC 443). Based on time-plasma concentration profile the pharmacokinetic parameters were determined by non-compartmental methods. Detectable plasma concentrations of ECZNP and enrofloxacin after IV administration persisted up to 36 h whereas after oral administration, plasma concentrations of ECZNP and enrofloxacin were detected up to 48 h. Cmax (μg.mL-1) of ECZNP 0.73±0.03 μg.mL-1 was significantly (P<0.01) lower than enrofloxacin 1.48±0.02 after oral administration, where as in IV route initial concentration (C0) of ECZNP 3.86±0.41 was significantly (P<0.01) lower than enrofloxacin 6.45±0.25. Important pharmacokinetic parameters obtained for ECZNP after its oral administration in group-I by non-compartmental analysis were: elimination rate constant (β) 0.06 h-1, elimination half-life (t1/2, β) 12.12±0.33 h, Cmax (μg.mL-1) 0.73±0.03, Tmax 4 h, area under time curve (AUC0-t μg.h.mL-1) 11.93±0.10, area under curve (AUCo-∞ μg.h.mL-1) 12.72±0.14, area under first moment curve (AUMCo-∞ μg.mL-1.h2) 208.39±3.59, volume of distribution (Vd L.kg-1) 4.12±0.08, total body clearance (ClB L.kg-1h-1) 0.24 and mean residence time (MRT) 16.38±0.15 h. In group-II the pharmacokinetic parameters of ECZNP for IV were: initial concentration of plasma (Co) 3.86±0.41 μg.mL1, Tmax 0.10±0.04 h, β 0.09±0.02 h-1, t1/2 β of 7.83±2.48 h, AUCo-t (μg.h.mL-1) 19.32±0.21, AUCo-∞ (μg.h.mL-1) 20.11±0.39, AUMCo-∞ (μg.mL-1.h2) 187.23±26.35, Vd (L.kg-1) 1.68±0.50, ClB (L.kg-1h-1) 0.15 and MRT 9.30±1.12 h. In group-III the pharmacokinetic parameters of enrofloxacin for oral were: Cmax (μg mL-1) 1.48±0.02 and Tmax 4.00±0.00 h, β 0.06±0.01 h-1, t½ β 11.85±1.42 h. AUCo-t (μg.h.mL-1) 24.05±0.91, AUCo-∞ (μg.h.mL-1) 25.59±1.40, AUMCo-∞ (μg.mL-1h2) 416.46±56.87, Vd (L.kg-1) 6.67±0.49, ClB (L.kg-1h-1) 0.39±0.02 and MRT (h) 16.22±1.36. In group-IV the pharmacokinetic parameters of enrofloxacin for intravenous (IV) were: Initial plasma concentration Co 6.45±0.25 μg.mL-1, Tmax 0.08 h, β 0.08±0.02 h-1, t½ β 9.11±2.20 h, AUCo-t (μg.h.mL-1) 32.92±0.97, AUCo-∞ (μg.h.mL-1) 34.40±1.18, AUMCo-∞ (μg.mL-1h2) 327.32±30.39, Vd (L.kg-1) 3.81±0.87, ClB (L.kg-1h-1) 0.29±0.01 and MRT 9.50±0.66 h. It was found that the Tmax, t½ β, MRT, and β were comparable after both oral and IV administration of ECZNP and enrofloxacin, Cmax of ECZNP was significantly lower (P<0.01) than enrofloxacin for oral, where as in IV route, the initial concentration (Co) of ECZNP was significantly lower (P<0.01) than enrofloxacin, AUCo-t, AUC0-∞, AUMC0-∞, Vd, and ClB of ECZNP were significantly lower (P<0.01) than enrofloxacin for both IV and oral route. In this study the bioavailability (F %) of ECZNP was 63.364 ± 1.372% and was significantly (P<0.05) lower compared to oral counterpart 74.886 ± 5.992%. The results of presents study indicated that bioavailability of ECZNP was significantly lower than enrofloxacin, which can be explained by the fact that the actual concentration of enrofloxacin in ECZNP was 6 mg/10 mg (60%), while the reference standard enrofloxacin was 99% W/V. Hence ECZNP was not comparable to reference enrofloxacin, in future studies this problem can be overcome by taking equal concentrations of ECZNP in enrofloxacin.
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