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The thousands of chemicals besides the soot of the cigarette inhaled for decades keep on acting on the various tissues and body systems causing changes in them ultimately leading to the irreparable damages system to function normally. Smoking can induce alteration in drug absorption, metabolism, degeneration, detoxification and drug excretion either in original form or in altered simple compound form. Therefore our aim was to investigate the effect of cigarette smoke on the pharmacokinetic profile of ofloxacin by using rabbits as experimental model. The tested group animals were exposed to cigarette smoke twice daily for 60 days. Ofloxacin was administered orally and samples of blood plasma were collected from each animal at different time intervals. Ofloxacin concentration in plasma samples is determined by microbiological assay using agar well diffusion method. Staphylococcus aureus was used as test organism. During the study on the drug interaction of cigarette smoke with ofloxacin, the pharmacokinetic parameters of ofloxacin such as AUC, Cmax, Tmax, t1/2, Vd and CL were altered due to the effect of cigarette smoke.