Norfloxacin dosing

Vibrio cholerae 01 or Doxycydine 300 mg oral single dose tetracycline 500 mg orally four times daily x 3 days or trimethoprim-0139 sulfamethoxazole DS tablet twice daily x 3 days norfloxacin 400 mg orally twice daily x 3 days or... 

Short-course therapy (3-day therapy) with trimethoprim-sulfamethoxazole or a fluoroquinolone (e.g., ciprofloxacin, levofloxacin, or norfloxacin) is superior to single-dose therapy for uncomplicated infection and... 

In attempts to improve the oral activity of norfloxacin, prodrug techniques have been employed. In an initial approach, the (5-methyl-2-oxo-l,3-diox-4-yl)-methyl group, which had been shown previously to be effective in a novel ampicillin prodrug, was investigated as a promoiety [ 109]. However, although the ester (77) liberates norfloxacin in the presence of mouse blood, after oral administration to mice, it was found that the blood levels of norfloxacin achieved are lower (approximately with respect to Cmax) than those achieved upon oral administration of an equimolar dose of norfloxacin, itself. This observation has been assumed to be due to an instability of this ester prior to absorption rather than an inability to liberate the parent drug after absorption. 

Norfloxacin - Absorption is rapid. Food or dairy products may decrease absorption. Steady-state norfloxacin levels will be attained within 2 days of dosing. Norfloxacin is eliminated through metabolism, biliary excretion, and renal excretion. Renal excretion occurs by glomerular filtration and tubular secretion. In healthy elderly volunteers, norfloxacin is eliminated more slowly because of decreased renal function. In patients with Ccr rates 30 mL/min/1.73 m or less, the renal elimination decreases so that the effective serum half-life is 6.5 hours dosage alteration is necessary. 

When norfloxacin was intramuscularly administered to calves, tissue concentrations were higher in kidney, liver, and muscle tissues at 4 h after the last dose (186). In body fluids other than bile and urine, norfloxacin concentration was lower than that in serum. None of the tissues sampled exceeded 1 ppm 24 h after the last administration at 72 h and 120 h after the last administration, highest concentrations in liver were 60 and 80 ppb, respectively. Norfloxacin could not be detected in muscle at 120 h postmedication. 

Carolyn et al. have reported two additional ultraviolet-absorbing metabolites in urine specimens [12]. The drug is partially metabolized in the liver by modification of the piperazinyl group. Oxo-ciprofloxacin and tV-acetyl-ciprofloxacin microbial activities are comparable to norfloxacin, and desethylene-ciprofloxacin is comparable to nalidixic acid for certain organisms. About 40-50% of an oral dose is excreted unchanged in the urine, and 15% as metabolites. Upto 70% of a parental dose may be excreted unchanged, and 10% as metabolites within 24 h [13, 14]. 

Fluoroquinolones are potent inhibitors of hepatic cytochrome P450 isozymes (150). They inhibit theophylline metabolism, and accumulation of theophylline has led to seizures (151). Theophylline clearance is reduced by about 10% by norfloxacin, 30% by ciprofloxacin, and 70% by enoxacin (152-162). In a comparison of grepa-floxacin (400 and 600 mg/day) and ciprofloxacin, increased theophylline concentrations associated with clinical symptoms were found with both doses of grepa-floxacin but not in patients taking ciprofloxacin (17). The dosage of theophylline should be reduced when a quino-lone is given. 

Swanson BN, Boppana VK, Vlasses PH, Rotmensch HH, Ferguson RK. Norfloxacin disposition after sequentially increasing oral doses. Antimicrob Agents Chemother 1983 23(2) 284-8. 

In children undergoing renal transplantation and receiving ciclosporin, the mean daily dose of ciclosporin needed to maintain adequate trough concentrations fell when patients were treated with norfloxacin for urinary tract infections (14). 

The tendency for certain fluoroquinolones (e.g.. norfloxacin and ciprofloxacin) in high doses to cau.se crysialluria in alkaline urine is, in part, due to the predominance of the comparatively less soluble zwiticrionic form. Solubility data presented for ofloxacin in the ISlh edition of the United Stiites Pharmacopoeia dramatically illustrate (he effect of pH on water solubility of compounds of the tluoroquinolone class. Thus, the. solubility of ofloxacin in water is 60 mg/ niL at pH values ranging from 2 to S. falls to 4 mg/mL at pH 7 (near the isoelectric point, pi), and rises to 303 mg/ mL at pH 9.8. 

The oral absorption of norfloxacin is rapid and reasonably cfftcient. Approximately 30% of an oral dose is excreted in the urine in 24 hours, along with 5 to 8% consisting of Ic.ss active metabolites. There is significant biliary excretion, with about 30% of the original drug appearing in the feces. 

Fosfomycin is a broad-spectrum, bactericidal antibacterial that inhibits the growth of E. coli. S. aureii.s, and Sernttia, Klebsiella, Cilmhucler, Enleroaiccus. and Enterohacter spp. at a concentration less than 64 mg/L. Currently fosfo-niycin i.s recommended as single-dose therapy for uncomplicated urinary tract infections. It possesses in vitro efficacy similar to that of norfloxacin and trimcthoprim-sulfamethox-a/.ole. 

Uncomplicated community-acquired urinary tract infection presents few problems with management. Drugs such as trimethoprim, ciprofloxacin and ampicillin are widely used. Cure rates are close to 100% for ciprofloxacin, about 80% for trimethoprim and about 50% for ampicillin—to which resistance has been steadily increasing. Treatment for 3 days is generally satisfactory and is usually accompanied by prompt control of symptoms. Single-dose therapy with amoxicillin 3 g has also been shown to be effective in selected individuals. Alternative agents include nitrofurantoin, nalidixic acid and norfloxacin, although these are not as well tolerated. Oral cephalosporins and co-amoxiclav are also used. 

Three-day courses of trimethoprim-sulfamethoxazole or a flu-oroquinolone (e.g., ciprofloxacin, levofloxacin, norfloxacin, or gatifloxacin) are superior to single-dose therapies." " The flnoro-qninolone moxifloxacin is not recommended for nse in UTIs owing to the inadequate urinary concentrations. The use of amoxiciUm and sulfonamides is not recommended because of the high incidence of resistant coli. For most adult females, short-course therapy is the treatment of choice for uncomplicated lower UTIs. Short-conrse therapy is inappropriate for patients who have had previons infections caused by resistant bacteria, for male patients, and for patients with complicated UTIs. If symptoms do not respond or recur, a urine cniture should be obtained and conventional therapy with a snitable agent instituted. ... 

The newer fluoroquinolones (ciprofloxacin, norfloxacin, enoxadn, pefloxacin, gatifloxadn and moxi-floxacin) have similar toxicities and incidence of adverse effects. In general, compared to other antibiotics, these are relatively safe agents [190]. Gastrointestinal side-effects are the most common (0.8 to 6.8% of patients), followed by central nervous system manifestations (0.9 to 1.8%), and skin reactions (0.6 to 2.4%). Rare cases of increased serum creatinine levels have been reported [203]. Indeed, in a study of 133 febrile episodes in neutropenic patients comparing the effectiveness and safety of high-dose oral ciprofloxacin versus azlociUin and netilmicin, there were no renal ad-... 

ABSORPTION, FATE, AND EXCRETION The quinolones are weU absorbed after oral administration and are widely distributed. Peak serum levels of the fluoroquinolones occur within 1-3 hours of an oral dose of 400 mg. Relatively low serum levels are reached with norfloxacin and limit its usefulness to the treatment of urinary tract infections. Food does not impair oral absorption but may delay the time to peak serum concentrations. Oral doses in adults are 200-400 mg every 12 hours for ofloxacin, 400 mg every 12 hours for norfloxacin and pefloxacin, and 250-750 mg every 12 hours for ciprofloxacin. Bioavailabrlity of the fluoroquinolones exceeds 50% for all agents and 95% for several. The serum half-lives range from 3 to 5 hours for norfloxacin and ciprofloxacin to 20 hours for sparfloxacin. The volume of distribution of quinolones is high, with concentrations in urine, kidney, lung and prostate tissue, stool, bUe, and macrophages and neutrophils higher than serum levels. Quinolone concentrations in CSF, bone, and prostatic fluid are lower than in serum. Pefloxacin and ofloxacin levels in ascites fluid approach serum levels, and ciprofloxacin, ofloxacin, and pefloxacin have been detected in human breast milk. 

Norfloxacin (Noroxin) Same mechanism. Covers enterics, P. aeruginosa (but not other pseudomonas strains), N. gonorrhea (including penicillin resistant strains), and S. aureus. Reduce dose with renal insufficiency. Urine levels high, serum levels low, not useful for infections outside urinary tract. 

Norfloxacin 3-4 h Crystalluria associated with doses above daily maximum and with alkaline urine. 

A study found that 300 mL of milk or yoghurt reduced the absorption and the peak plasma levels of a single 200-mg dose of norfloxacin by roughly... 

---