MODIFICATION OF DISPOSITION KINETICS OF AZITHROMYCIN BY TOLFENAMIC ACID AND ENDOTOXIN INDUCED FEVER IN GOATS
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Date
41075
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Kerala Veterinary and animal science university, Pookode
Abstract
Azithromycin is the first of a class of antimicrobial agent belonging to the class azalides. The aim of the present study was to investigate the alteration of disposition kinetics of azithromycin in the presence of tolfenamic acid in both afebrile and endotoxin-induced febrile conditions in goats following intravenous route of administration. So far no pharmacokinetic data is available on the interaction kinetics of azithromycin and tolfenamic acid in any animal species. Azithromycin alone, azithromycin with tolfenamic acid were administered intravenously (i/v) to normal healthy afebrile goats (I and II). To febrile group of III and IV, azithromycin alone, azithromycin with tolfenamic acid were administered intravenously one hour after the injection of endotoxin which was to induce the febrile condition. Blood samples of each goat were collected at 0 (control), 5, 10, 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hour of drug administration for analysis of azithromycin by HPLC. The analysis of azithromycin was carried out using the mobile phase of 0.045M potassium dihydrogen phosphate(pH 3):methanol (20:80) on a C18 column with a flow rate of 2ml.min-1 and column temperature set at 500C ,the photodiode array detector (PDA) set at 210nm was used for detection.The retention time obtained for azithromycin was 3.7min.The response linearity of azithromycin was checked from 100-2000ppm and got a correlation coefficient of 0.976 for the concentration analysed.
Azithromycin alone blood concentrations versus time following intravenous administration of both afebrile and febrile condition were fitted to three compartment model.The various kinetic parameters were determined as per standard formulae by Gibbaldi and Perrier (1982).( C0B afebrile and febrile 2031991 and 277.17 μg.ml-1respectively, Cl afebrile and febrile 0.045 and 0.08 L.kg−1.h−1 respectively,Vβ afebrile and febrile 2.18 and 3.58L.kg-1). Azithromycin along with tolfenamic acid in both afebrile and febrile condition followed a non compartment model. (t1/2 afebrile and febrile 18.95 and 21.66 hours respectively, MRT afebrile and febrile 37.99 hours and 41.81hours respectively, tmax afebrile and febrile 24 and 36 hour respectively, Cmax afebrile and febrile 5211 and 3155.87 mg.L-1respectively).
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