EFFECT OF SINGLE AND SHORT-TERM ADMINISTRATION OF QUERCETIN ON THE PHARMACOKINETICS OF ENROFLOXACIN IN BROILER CHICKENS
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Date
2019-01
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SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517502. (A.P.) INDIA
Abstract
An experimental study on thirty broiler chicken weighing about 2.0 kg was conducted to evaluate the pharmacokinetics of enrofloxacin along with quercetin either as co- administration or as short - term pre - treatment. The birds were divided into 3 groups of 10 birds each and were randomly administered enrofloxacin orally at dose rate of 10 mg/kg body weight (group1), quercetin followed by enrofloxacin sixty minutes later (group 2) and quercetin for 10 days with enrofloxacin sixty minutes after the quercetin on the 10th day. Both enrofloxacin and quercetin were given orally at the dose rate of 10 and 15 mg/kg body weight (group 3). Blood samples from the treated groups were collected from either left (or) right tarsal veins 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 and analysed for enrofloxacin by HPLC method. The HPLC method applied was found table accurate and precise and exhibited acceptable recovery statistics from plasma spiked samples. Enrofloxacin was detected in the birds of all three groups at all the tested time points
The pharmacokinetic parameters observed in group 1 birds were in accordance with the previous reports on the pharmacokinetics of enrofloxacin in broiler chickens. Elimination rate constant, β in group 2 (0.047±0.004 1/h) birds, in which quercetin was co-administrated with enrofloxacin, was significantly lower when compared to group 1(0.061±0.001 1/h) and 3 (0.079±0.004 1/h) birds. This was further reflected in singnificaly increased elimination half-life, t1/2 (15.642±1.085 h) in group 2 when compared with group 1(11.437±0.248 h) and 3 (9.105±0.641 h) birds. This could be attributed to the ability of quercetin to inhibit the hepatic metabolizing enzymes like CYP3A4 and efflux proteins like P-glycoprotein. Slowdown in the metabolic inactivation of enrofloxacin with subsequently lowered elimination from the body might have resulted in increased half-life. AUC0-∞ observed in group 2 (44.437±2.729 μg/ml.h) was significantly higher than that of group 3 (30.393±2.111 μg/ml.h), which indicated that the extent of absorption of enrofloxacin was high when co-administered orally with quercetin compared to enrofloxacin oral administration after short-term quercetin pre-treatment. The area under first moment curve (AUMC) and mean resident time (MRT) recorded in group 2 (1067.707±81.605 μg/ml.h2 and 23.876±1.030 h) was significantly higher than those recorded in groups 1 (654.193±65.964 μg/ml.h2 and 17.077±0.364 h) and 3 (480.580±53.213 μg/ml.h2 and 15.636±1.076 h).
The clearance observed in group 2 (0.234±0.016 L/kg/h) was significantly lower when compared to group 3 (0.347±0.030 L/kg/h) but not with group 1(0.282±0.024 L/kg/h).
It was observed from the study that enrofloxacin co-administered with quercetin in group 2 has exhibited higher t1/2, AUC0-∞, AUMC and MRT values. On the other hand, short – term treatment with quercetin in group 3 resulted in significantly higher elimination rate constant (β), significantly lower (t1/2), apparently lower Cmax, apparently lower AUC0-t, significantly lower AUC0-∞, significantly lower AUMC, significantly lower MRT and significantly increased ClB when compared to those observed in quercetin co-administrated birds. These results indicate that though co-administration of single dose quercetin increased the half-life, area under curve and mean resident time of enrofloxacin, repeated administration of quercetin actually reduced the above kinetic parameters of enrofloxacin. Hence in the present study, it is possible that increased bioavailability of enrofloxacin with single dose quercetin might have resulted from inhibition of P-gp in the intestine. On the other hand the decreased bioavailability of enrofloxacin with repeated quercetin treatment might have resulted from induction of CYP3A activity. It can be concluded from the present study that single dose co – administration of quercetin enhances the bioavailability of enrofloxacin, while repeated administration of quercetin reduces the same.
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