Norfloxacin pharmacokinetics

The effect of these changes to ciprofloxacin and norfloxacin pharmacokinetics on the control of infection is uncertain but until the situation is clear patients should be advised not to take these dairy products within 1 to 2 hours of either ciprofloxacin or norfloxacin to prevent admixture in the gut. The slight reduction in gatifloxacin levels is probably not clinically relevant. 

A Anadon, MR Martmez-Larranaga, MJ Diaz, R Fernandez, MA Martinez, MC Fernandez. Pharmacokinetics and tissue residues of norfloxacin and its V-desethyl- and oxo-metabolites in healthy pigs. J Vet Pharmacol Ther 18 220-225, 1995. 

Introduction of the first fluorinated quinolone, norfloxacin [nor FLOX a sin], has been rapidly followed by new members of this class. These agents are totally synthetic and are closely related structurally to an earlier quinolone, nalidixic acid [nal i DIX ik]. The principal member of this group is ciprofloxacin [sip ro FLOX a sin], which has the widest clinical application. Other antibiotics in this group available in the United States are primarily employed to treat urinary infections (Figure 32.1). It seems likely that the size of this class of antibiotics will increase due to its wide antibacterial spectrum, favorable pharmacokinetic properties and relative lack of adverse reactions. Unfortunately, their overuse has already led to the emergence of resistant strains resulting in limitations to their clinical usefulness. 

The breakthrough in the development of quinolones came with the appearance of norfloxacin 6 [19], a second-generation quinolone which combined a 6-fluorine substituent with a piperazine ring in the 7-position of the basic compound. Additional quinolones then followed in rapid succession pefloxacin [20], enoxacin [21] and fleroxacin [22] (Fig. 14.5). Particular mention must be made of ciprofloxacin 8 [23-25], ofloxacin 5 [26,27] and its active enantiomer levofloxacin 7 [28]. These quinolones have a broad spectrum of activity, which also includes Gram-positive bacteria and Pseudomonas aeruginosa, as well as favorable pharmacokinetics. The rapid absorption of these compounds from the gastrointestinal tract and their effective tissue penetration also allows them to be used for the treatment of systemic infections. 

Okhamafe, A.O. Akerele, J.O. Chukuka, C.S. Pharmacokinetic interactions of norfloxacin with some metallic medicinal agents. UP 1991, 68, 11-18. 

Co-administration of fenbufen and fluoroquinolones has been associated with seizures (141). The structure at the 7-position greatly affects the risk of NSAID-potentiated nervous system effects. Fluoroquinolones with unsubstituted piperazinyl rings (ciprofloxacin, enox-acin, and norfloxacin) have a strong interaction with NSAIDs (142). The increased risk of seizures is not caused by increased serum concentrations of fluoroquinolones, since their pharmacokinetics are not altered by NSAIDs (143). The mechanism has been suggested to be facilitation by fenbufen of the fluoroquinolone-induced inhibition of GABAa receptor function in the hippocampus and frontal cortex (144). 

Bowles SK, Popovski Z, Rybak MJ, Beckman HB, Edwards DJ. Effect of norfloxacin on theophylline pharmacokinetics at steady state. Antimicrob Agents Chemother 1988 32(4) 510-12. 

Ho G, Tierney MG, Dales RE. Evaluation of the effect of norfloxacin on the pharmacokinetics of theophylline. Clin Pharmacol Ther 1988 44(l) 35-8. 

Patients who received bone marrow [267] and heart transplants [268] did not show any evidence of nephrotoxicity when receiving ciprofloxacin. Contrary to previous preliminary findings [253,269], more recent data suggest lack of relevant pharmacokinetic interaction of ciprofloxacin with cyclosporine[268]. Similar preliminary claims of norfloxacin [270], ofloxacin [271], and pefloxacin-cyclosporine [272] interactions have been made. 

Laczay, P., Semjen, G., Nagy, G. Lehel, J. (1998) Comparative studies on the pharmacokinetics of norfloxacin in chickens, turkeys and geese after a single oral administration. Journal of Veterinary Pharmacology and Therapeutics, 21,161-164. 

Lehto, P Kivisto, K.T. Effect of sucralfate on absorption of norfloxacin and ofloxacin. Antimicro6.Agents Chemother., 1994, 38, 248-251 [extracted norfloxacin plasma urine LOQ 100 ng/mL pharmacokinetics]... 

A. Classification and Pharmacokinetics The original fluoroquinolone is norfloxacin others in the group include ciprofloxacin, ofloxacin, levofloxadn, lomefloxacin, and sparfloxadn. 

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. 

Oldiamafe AO, jA erele JO, Qiukuka CS. Pharmacokinetic interactions of norfloxacin with some metallic me[Pg.332]

Most studies show that the quinolones have, at most, a small, clinically insigniilcant effect on the pharmacokinetics and pharmacodynamics of warfarin. Despite this, increased effects and even bleeding have been seen quite unpredictably in isolated cases in patients taking warfarin with ciprofloxacin, gatifloxacin, levo-floxacin, moxifloxacin, nalidixic acid, norfloxacin or ofloxacin or while taking acenocoumarol when given nalidixic acid, norfloxacin or pefloxacin, or phenprocoumon with norfloxacin. Fur-... 

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. ... 

S. Wallis, B. Charles, L. Gahan, L. Filippich, M. Bredhauer, and P. Duckworth, Interaction of norfloxacin with divalent and trivalent pharmaceutical cations. In vitro complexation and in vivo pharmacokinetic studies in the dog, J. Pharm. ScL, 85, 803-809 (1996). 

Replacement of N-ethyl group with NHCH3 leads to a highly effective drug amifloxacin. Although it has not exhibited in vitro tests a considerable advantage in comparison with norfloxacin and pefloxacin, it shows a better pharmacokinetic profile, being equally active in both oral and parenteral administration. 

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