Norfloxacin Caffeine

Caffeine [P] Ciprofloxacin, enoxacin, pipedemic acid, and to a lesser extent, norfloxacin, inhibit caffeine metabolism. 

The interaction between the quinolone antibacterials and CYP1A2 has been studied in some depth for enoxacin and pefloxacin. Both compounds have been shown to inhibit CYPlA2-mediated metabolism of caffeine in vitro (49). This in vitro inhibition translated into a twofold decrease in caffeine clearance by pefloxacin and a sixfold decrease in clearance by enoxacin (50). Because pefloxacin undergoes N-demethylation to norfloxacin (51) and norfloxacin is much more potent as an inhibitor than pefloxacin (50), the observed in vivo interaction seen for pefloxacin may, in part, be due to norfloxacin. Many other quinolone antibacterial agents have been investigated for their interaction with theophylline, and ciprofloxacin has also been shown to have notable inhibitory effects (52). 

Noninterfering adenosine, albuterol, alphenal, aspirin, caffeine, carbamazepine, cefazo-lin, cephalexin, cephalothin, cimetidine, ciprofloxacin, claforan, desipramine, enoxacin, fleroxacin, furosemide, hydralazine, hydrochlorothiazide, minoxidil, norfloxacin, pheny-toin, propafenone, sulindac, teicoplanin, theophylline, vancomycin Interfering some indocyanine green impurities... 

B. Pharmacokinetics. Caffeine is rapidly and completely absorbed orally with a volume of distribution of 0.7-0.8 L/kg. Its elimination half-life is approximately 4-6 hours but can range from 3 hours in healthy smokers to 10 hours in non-smokers after overdose the half-life may be as long as 15 hours. In infants less than 2-3 months old, metabolism is extremely slow and the half-life may exceed 24 hours. (See also Table 11-59.) Caffeine is metabolized in the liver by cytochrome P-450, primarily the CPY 1A2 isoenzyme, and is subject to several potential drug interactions, including inhibition by estrogens, cimeti-dine, norfloxacin, and alcohol. Tobacco (and marijhuana) smoking accelerates caffeine metabolism. 

Enoxacin markedly increases caffeine levels. The effects of caffeine derived from drinks such as tea, coffee or cola, would be expected to be increased. Pipemidic acid interacts to a lesser extent, and ciprofloxacin, norfloxacin and pefloxacin interact less still Fleroxacin, lomefloxacin, ofloxacin, rufloxacin, and trovafloxacin appear not to interact. 

Established interactions. Based on the results of two studies, on a scale of 100 to 0, the relative potencies of these quinolones as inhibitors of caffeine elimination have been determined as follows enoxacin 100, pipemidic acid 29, ciprofloxacin 11, norfloxacin 9 and ofloxacin 0. From further studies, clinafloxacin appears to be similar to enoxacin (profound effect), pefloxacin to norfloxacin (to which it is metabolised modest effect), and fleroxacin, lomefloxacin, rufloxacin, and trovafloxacin appear to behave like ofloxacin (no effect). Patients taking enoxacin might be expected to experience an increase in the effects of caffeine (such as headache, jitteriness, restlessness, insomnia) if, for example, they continue to drink their usual amounts of caffeine-containing drinks (tea, coffee, cola drinks, etc.). They should be warned to cut out or reduce their intake of caffeine if this occurs. The authors of one report suggest that patients with hepatic disorders, cardiac arrhythmias or latent epilepsy should avoid caffeine if they take enoxacin for one week or more. The effects of pipemidic acid arc less, and those of ciprofloxacin, norfloxacin and pefloxacin arc probably of little or no clinical importance. Fleroxacin, lomefloxacin, ofloxacin, rufloxacin, and trovafloxacin do not interact. 

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