Norfloxacin 416 Subject

The data on the adverse reactions of the fluoroquinolones which have received the most extensive clinical evaluation (ciprofloxacin, ofloxacin, pefloxacin, norfloxacin and enoxacin), involving about 30,000 patients, have been the subject of a review [54a], An important point noted in this review involves the difficulty in detecting an important severe adverse reaction if it is of relatively low frequency, until there has been a very large patient exposure (some examples are provided in which at least 150,000-300,000 exposures would be required to observe the importance of side-effects, resulting in an alert, which have been discovered with specific drugs). However, the majority of side-effects observed thus far with the fluoroquinolones have been minor,... 

The syntheses of the fluoroquinolones were completed by subjecting the corresponding esters to basic hydrolysis. Treatment of 15a and 15b with 2N sodium hydroxide solution for two hours at reflux resulted in near quantitative yields of Norfloxacin (1) and the N-methylpiperazine derivative 16. ... 

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. 

Famotidine given 8 hours before norfloxacin significantly reduced its maximum serum concentrations in 6 healthy subjects, but the AUC and urinary recovery rate were unchanged. ... 

In 8 healthy subjects ferrous sulfate reduced the AUC and maximum serum levels of a single 400-mg dose of norfloxacin by 73% and 75%, respectively. Ferrous sulfate caused a 51% reduction in the norfloxacin AUC in another study, and a 97% reduction in bioavailability in a further single dose study. The same authors also found that both ferrous... 

The mean 12-hour urinary recovery of norfloxacin 200 mg was reduced by about half in 5 subjects vflienthey were given probenecid 1 g. Norfloxacin serum concentrations were unaffected. ... 

A study in 8 healthy subjects found that sucralfate 1 g four times daily reduced the AUC of a single 400-mg dose of norfloxacin by 98%, when fak-en with the sucralfate, and by 42% when taken 2 hours after the sucralfate. Another study found a reduction of 91% in the AUC of norfloxacin 400 mg when it was taken with sucralfate 1 g, but no reduction when it was taken 2 hours before sucralfate. ... 

In 10 healthy subjects norfloxacin 400 mg twice daily for 9 days was found not to alter either the pharmacokinetics or anticoagulant effects of a single 30-mg dose of warfarin given on day 4. ... 

Ofloxacin 200 mg daily for 7 days did not signifrcantly affect the prothrombin times of 7 healthy subjects stabilised on phenprocoumon. In a population-based cohort study, there were no cases of over-anticoagu-lation (USTR greater than 6) in patients taking acenocoumarol or phenprocoumon with ofloxacin (33 received ofloxacin. Note that this study did find an increased risk for norfloxacin, see (j) above. Furthermore, for the period December 1990 to January 2004, Health Canada had not received any reports of suspected coagulation disorders associated with ofloxacin and warfarin. ... 

A study in 11 healthy subjects found that norfloxacin 400 mg twice daily reduced the AUC of a single 1-g oral dose of mycophenolate mofetil given two hours after the antibacterial on day 4 by 10%. The AUC of the glucuronide metabolite was also reduced by 10%. When norfloxacin 400 mg twice daily was also given, the AUC of mycophenolate and its glucuronide metabolite were reduced by 33% and 41%, respectively. This interaction was thought to be due to interference of the enterohepatic recirculation of mycophenolate by the antibacterials. There appear to be no further clinical reports of an interaction between these antibacterials and mycophenolate. The changes with norfloxacin alone were modest, and unlikely to be... 

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