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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, K
The 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.
Open Access
SUB-ACUTE TOXICITY STUDIES ON UNPROCESSED AND PROCESSED PONGAMIA PINNATA SEED CAKE IN RATS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2013-02) SIRISHA, K; KALA KUMAR, B.D.P(MAJOR); GOPALA REDDY, A; MADHAVA RAO, T; ANJANEYULU, Y
ABSTRACT : The present study was aimed to evaluate the toxic and protective effects of unprocessed and processed Pongamia pinnata seed cake in rats, which were divided into 3 groups as follows: Group 1: sham control, group 2: unprocessed Pongamia pinnata seed cake included at the level of 9% in the feed (toxic control) and group 3: processed (solvent extracted-isopropyl alcohol) Pongamia pinnata seed cake (detoxified cake) included at the level of 9% in the feed. Average body weights were recorded at weekly intervals and on 28th day, organs were collected for estimation of TBARS, protein carbonyls and GSH in kidney, liver and testes homogenates and estimation of epididymal sperm count from testes collected. Sero-biochemical parameters like ALT, total proteins & globulins, total cholesterol, HDL & LDL cholesterol, creatinine and LDH were estimated at fortnight intervals. Haemotological parameters (RBC, WBC, Hb and PCV) were also estimated at fortnight intervals. Serum troponins, PHA assay and testicular LDH were estimated at the end of the experiment. Histopathology of heart, liver, kidney, spleen and testis was also studied at the end. Mean body weight gain, GSH, total proteins and globulins, PHA assay and sperm count were significantly (P < 0.05) decreased in toxic control group (group 2), while TBARS, protein carbonyls, serum LDH, intra-testicular LDH, serum ALT, creatinine, total cholesterol and serum troponins were significantly (P < 0.05) increased in group 2. There was no significant difference in TEC, TLC, Hb, PCV, HDL cholesterol, LDL cholesterol, mean body weight gain (in the 1st week) in group 2. Group 1 did not reveal any abnormalities on histopathology. Group 2 showed interfibrillar haemorrhages, congestion and edema with disruption of cardiac myofibres in heart, marked degenerative changes in tubular epithelial cells and marked dilatation of tubules in kidney, marked central vein congestion and marked bile duct hyperplasia in liver, congestion and thickening of trabecular arteries in spleen and finally marked congestion and edema with disrupted cell wall in seminiferous tubules of testes. Group 3 showed mild lesions in heart, kidney, liver, spleen and testis. From this study, it is concluded that unprocessed Pongamia pinnata seed cake induces toxicity to heart, kidney, liver, spleen and testes, and group 3 showed restoration in all the parameters studied, suggesting reduced toxic potential of processed seed cake.
Open Access
A STUDY ON THE TERATOGENIC EFFECTS AND ORGAN TOXICITY OF NIMESULIDE AT DIFFERENT DOSE LEVELS IN PREGNANT AND PROGENY RATS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2011-10) SWAPNIL VIJAYKUMAR JINTPURE; USHA RANI, M(MAJOR); GOPALA REDDY, A; ANJANEYULU, Y
ABSTRACT: The present study was aimed to evaluate the teratogenic effects and organ toxicity in the dams and their progeny treated with nimesulide in gestation period at different dose levels. Seventy two female albino rats of Sprague dawley strain were divided into 3 groups and treated as follows. Group 1 served as control, group 2 received nimesulide @ 20 mg/kg body weight and group 3 received nimesulide @ 60 mg/kg body weight via intramuscular route from day 7th to 17th day of gestation. In each group, half of the pregnant rats were subjected to caessarian section on 19th day of gestation (caessarian group namely “A”) and the remaining half of the pregnant rats were allowed for normal parturition (normal parturition group namely “B”). Average body weights were recorded at weekly intervals in dams of caessarian, normal parturition group and in progeny of normal parturition group up to weaning day. On 19th day, half of pregnant dams in each groups were subjected to caessarian for uterine weights with progeny, resorption sites, inborn progeny body weight, litter size, live and dead numbers, male: female progeny numbers, skeletal staining of progeny with Alizarin-Red S, Alcian blue-Alizarin Red S stains and soft tissue developmental anomalies. The remaining half, allowed for normal parturition and recorded inborn progeny body weights, litter size, live-dead numbers, male: female progeny numbers and other abnormalities, if any. Serum biochemical profiles (Albumin, ALP, ALT, AST, BUN, creatinine, GGT and total protein) were recorded on 19th day of gestation in dams of caessarian group and the same serum biochemical profiles and haematology (RBC, WBC and haemoglobin) was recorded on post natal day 21 in progeny of normal parturition group. TBARS and GSH were estimated on 19th day in liver and kidney homogenates. Histopathology of kidney, liver, stomach and ovary were studied in dams of caessarian group on 19th day and liver, kidney and heart in progeny of normal parturition group on weaning day. The study showed no evidence of teratogenicity by skeletal staining, uterine weights with progeny, resorption sites, litter size, inborn progeny body weights, male: female progeny numbers, live and dead numbers, and weekly body weights in progeny upto weaning. There was a significant difference in serum biochemical profiles of dams and was more evident in nimesulide treated at 60 mg/kg body weight. Further, there was no significant difference in the haematological parameters and serum biochemical profiles of progeny except an increase in BUN and creatinine, which was more evident in group 3 as compared to groups 2 and 1. Treatment with nimesulide at higher dose induced oxidative stress and tissue damage of liver and kidney as evident from increased levels of MDA and decreased levels of GSH, histopathology of liver, kidney and stomach of dams and kidney of progeny of normal parturition group. It is concluded that nimesulide at 60 mg/kg body weight in pregnant dams showed more significant damage to liver and kidney as from light microscopic findings of liver, kidney, stomach and ovary as compared to the dose of 20 mg/kg body weight and control.
Open Access
PROTECTIVE EFFECT OF VITAMIN E IN DOXORUBICIN-INDUCED TOXICITY IN RATS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2010-08) SHIVAKUMAR, P; USHA RANI, M(MAJOR); GOPALA REDDY, A; ANJANEYULU, Y
ABSTRACT: The present study was aimed to evaluate the protective effect of vitamin E in doxorubicin-induced toxicity in rats, which were divided into 4 groups and treated as follows: Group 1: sham control, 2: doxorubicin control, 3: doxorubicin + vit-E @150 mg/kg b. wt and 4: doxorubicin + vit-E @ 500 mg/kg b. wt Average body weights were recorded at weekly intervals and organ weights were recorded at the time of sacrifice. On 28th day, organs were collected for estimation of TBARS, protein carbonyls and GSH in tissue homogenates. Activity of Na+-K+ ATPase , Mg2+ATPase and CYP450 of liver, intra-testicular LDH, serum troponins, creatinine, LDH and AST were also estimated, besides haematology at the end of experiment on 28th day. Histopathology of heart, liver, kidney and testes was also studied at the end. Body weight gain, relative organ weight, RBC, WBC, Hb, PCV, GSH, CYP450, Na+/K+ ATPase and Mg2+ATPase were significantly (P < 0.05) decreased in doxorubicin group, while TBARS, protein carbonyls, serum LDH, intra-testicular LDH, serum AST, creatinine and serum troponins were significantly (P < 0.05) increased in group 2. Group 1 did not reveal any abnormalities on histopathology. Group 2 (doxorubicin) showed marked congestion and degenerative changes in heart, kidney, liver and testis. Vitamin E-treated groups (3 and 4) showed improvement in all the parameters studied, though it was marked with vitamin E @ 500 mg/Kg. From this study, it is concluded that doxorubicin induces toxicity to heart, kidney, liver and testes, and these effects can be reverted by vitamin –E administration in a dose-dependent manner.
Open Access
PROTECTIVE EFFECT OF N-ACETYL CYSTEINE AGAINST ARSENIC-INDUCED TOXICITY IN RATS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2010-06) HEMALATHA, P; GOPALA REDDY, A(MAJOR); USHA RANI, M; ANAND KUMAR, A; RAMANA REDDY, Y
ABSTRACT: N-acetyl cysteine was evaluated against arsenic-induced toxicity in rats. The Wistar rats were divided into 4 groups and treated as follows: Group 1: sham control, 2: arsenic control, 3: N-Acetyl cysteine (NAC) pre-treatment for two weeks followed by arsenic + NAC and 4: arsenic + NAC. Average body weights were recorded at weekly intervals and testes weights were recorded at the time of sacrifice. On 29th day, organs were collected for estimation of TBARS, protein carbonyls and GSH in tissue homogenates. Activity of Na+-K+ ATPase , Mg2+ATPase and CYP450 of liver, intra-testicular LDH, serum creatinine, and serum LDH were also estimated. Histopathology of heart, liver, kidney, testis, lung, intestine and stomach was also studied at the end. Body weight gain, relative testis weight, GSH, CYP450, Na+/K+ ATPase and Mg2+ATPase were significantly (P < 0.05) decreased, while TBARS, protein carbonyls, serum LDH, intra-testicular LDH and serum creatinine were significantly (P < 0.05) increased in group 2 as compared to other groups. Group 1 did not reveal any abnormalities on histopathology. Group 2 (arsenic control) showed marked degenerative changes in heart, kidney, liver, testis, lung, intestine and stomach. NAC-treated groups (3 and 4) showed improvement in all the parameters studied, though it was marked with NAC pre-treatment. From this study, it is concluded that arsenic induces toxicity to heart, kidney, liver, testis, lung, intestine and stomach, and these effects can be reverted by NAC administration.
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, P
ABSTRACT : 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.
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, V
ABSTRACT: 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.
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, V
ABSTRACT: 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.
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, V
ABSTRACT: 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.

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