Studies on the Pharmacokinetic Interaction between Meloxicam and Quercetin, a CYP2C9 and CYP3A4 Inhibiting Flavonoid, in Rabbits
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Date
2010-07
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Sri Venkateswara Veterinary University, TIRUPATI – 517 502,A.P
Abstract
ABSTRACT :
The present study was aimed to investigate the pharmacokinetic interaction between meloxicam and quercetin, a CYP2C9 and CYP 3A4 inhibiting flavonoid, in rabbits. Fifteen male rabbits were divided into three groups with five animals in each group and the treatment was given as follows: group I (Control) received meloxicam alone @ 1.5 mg/kg b.wt orally; Group II received meloxicam @ 1.5 mg/kg b.wt orally 30 minutes after the pretreatment with quercetin orally @ 10mg/kg b.wt; group III received meloxicam @ 1.5 mg/kg b.wt orally 30 minutes after the pretreatment with quercetin orally @ 20mg/kg b.wt. Blood was collected by veinipuncture at 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 h. Plasma was separated by centrifuging the blood and was subjected to HPLC assay for estimation of meloxicam. Important pharmacokinetic parameters after non compartmental analysis were t1/2B, 14.52 ± 4.4 h; ClB, 0.1 ± 0.01 L.kg-1.h-1; AUC0-∞,16.02 ± 1.95 μg.h.mL-1; Vdss,1.97 ± 0.24 L.kg-1: and MRT, 21.89±5.32 h in group I, t1/2B, 11.46 ± 1.62 h; ClB, 0.1± 0.01 L.kg-1.h-1; AUC0-∞,15.40 ± 1.18 μg.h.mL-1; Vdss,1.83 ± 0.24 L.kg-1: and MRT, 18.1 ± 1.8 h in group II and t1/2B, 9.93 ± 0.59 h; ClB, 0.07 ± 0.01 L.kg-1.h-1; AUC0-∞,21.08 ± 1.36 μg.h.mL-1; Vdss,1.14 ± 0.11 L.kg-1: and MRT, 15.58 ± 0.64 h in group III.
The results in present study indicate that the quercetin pretreatment at 10 mg.kg-1 has no significant effect on the pharmacokinetic profile of meloxicam in rabbits where as the quercetin pretreatment at 20 mg.kg-1 has affected the pharmacokinetic parameters.
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Keywords
pharmacokinetic interaction; meloxicam; quercetin; rabbits