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Subject: Veterinary Pharmacology × Author: KASTURI DEVI, K × End date: 2018 × Start date: 2010 × Thesis Type: M.V.Sc. ×
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    ThesisItemOpen Access
    Pharmacokinetic interaction studies between breast cancer resistance protein (BCRP) inhibiting flavonoids and ciprofloxacin in rats
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI – 517 502. (A.P) INDIA, 2010-07) KASTURI DEVI, K; SRINIVASA RAO, G (Major); RAVI KUMAR, P; ANANDA KUMAR, P
    ABSTRACT : Pharmacokinetic interaction between ciprofloxacin, an antibacterial fluoroquinolone that was described as a substrate for breast cancer resistance protein (BCRP) and BCRP inhibiting flavonoids curcumin and quercetin in rats was investigated in the present study. Male Wistar albino rats, weighing about 200-250g were randomly divided into three groups consisting six rats in each group. Rats in group I (control) received ciprofloxacin alone (10 mg.kg-1 PO). Group II received curcumin (400 mg.kg-1, PO) 30 min prior to administration of ciprofloxacin. Similarly Group III received ciprofloxacin 30 min after pretreatment with quercetin (20 mg.kg-1, PO). Rats were anaesthetized after ciprofloxacin administration for blood collection with a Xylazine-Ketamine combination. Blood samples were collected from jugular vein and tail clipping at predetermined time intervals prior to and at 0.33, 0.67, 1, 1.5, 2, 4, 6, 8 and 12 h time intervals after administration of ciprofloxacin. Plasma was separated by centrifuging at 3000 RPM for 10 min and stored at -200c until analyzed for ciprofloxacin by microbiological assay using Escherichia coli (ATCC 25922). Based on plasma concentrations the pharmacokinetic parameters were determined by non compartmental methods. Detectable plasma concentrations of ciprofloxacin in rats persisted upto 6 h when ciprofloxacin was given alone where as ciprofloxacin was detectable upto 8 h in both curcumin and quercetin pretreated rats. Cmax of ciprofloxacin in group I was 1.12±0.18 μg.mL-1. There was significant increase in Cmax of ciprofloxacin in both curcumin (Group II: 1.74±0.052 μg.mL-1) and quercetin (Group III: 1.99±0.1 μg.mL-1) pretreated rats. Important pharmacokinetic parameters obtained for ciprofloxacin after its oral administration in group I (control) by non compartmental analyses were: elimination rate constant (β) 0.40±0.049 h-1; elimination half life (t½β) 1.85±0.22 h; area under plasma concentration time curve (AUC0-∞) 2.38±0.31 μg.h.mL-1 ; area under first moment curve (AUMC0-∞) 6.26±1.24 μg.h 2.mL-1; steady state volume of distribution (Vdss) 10.98±0.78 L.kg-1; total body clearance (ClB) 4.56±0.55 L.kg-1.h -1; and Mean residence time (MRT) 2.52±0.2 h. In group II the pharmacokinetic parameters for ciprofloxacin in curcumin pretreated rats were : β, 0.237±0.037 h-1; t½β, 3.49±0.77 h; AUC0-∞, 6.03±1.01 μg.h.mL-1; AUMC0-∞, 35.37±15.10 μg.h 2.mL-1; Vdss, 8.31±0.82 L.kg-1; ClB, 1.83±0.22 L.kg-1.h -1 ; MRT, 5.03±1.06 h. It was found that there was a significant increase (p<0.01) in Cmax, , longer MRT and t½β indicated the tendency of ciprofloxacin retention in plasma of rats when pretreated with curcumin . In group III pharmacokinetic parameters for ciprofloxacin in quercetin pretreated rats were: β, 0.298±0.029 h-1; t½β, 2.00±0.38 h; AUC0-∞, 4.55±0.27 μg.h.mL-1; AUMC0-∞, 13.19±1.14 μg.h 2.mL-1; Vdss, 6.48±0.51 L.kg-1; ClB, 2.23±0.14 L.kg-1.h -1 ; MRT, 2.88±0.15 h. A significant increase (P<0.01) in Cmax, AUC0-∞ and a significant decrease (p<0.01) in clearance for ciprofloxacin was found in rats when pretreated with quercetin. Thus results of the present study indicated that pretreatment with curcumin and quercetin significantly increased the concentrations of ciprofloxacin in rats. Thus it is evident that BCRP inhibiting flavonoids like curcumin and quercetin enhance the retention time of ciprofloxacin in plasma, which in turn improves the clinical efficacy of ciprofloxacin against susceptible bacterial infections.