Fluoroquinolone solubility

Norfloxacin is a new water-soluble fluoroquinolone registered for veterinary use in several countries. It is commercially available as a dry powder for medication of drinking water and as a sterile injectable solution (182). 

Quinolone carboxylic acid antibacterials are synthetic compounds whose basic nuclear structure includes a quinolone ring and a carboxylic acid group. Fluoroquinolones are second-generation quinolones that contain in their molecule a fluorine and a piperazine ring. Quinolones are amphoteric compounds slightly soluble in polar solvents such as water, and insoluble in nonpolar solvents such as benzene and hexane. Most of these drugs are fluorescent and are quite stable in aqueous solution toward light, except miloxacin, which is reported to be unstable. 

The fluoroquinolones are extremely lipid soluble and distribute well. The Vj of enrofloxacin is 2-51/kg in most species. Tissue concentrations greatly exceed plasma concentrations during therapy. Extremely high concentrations are achieved in the kidneys, urine, liver and bile. After mulHple p.o. doses, urine, endometrial tissue and synovial fluid concentrations in horses are higher than serum concentrations. Therapeutic concentrations may be achieved in the CSF. High concentrations occur in milk. The protein binding is low (22%). 

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. 

Ross and Riley (11) reported an HPLC method for determination of solubilities of lomefloxacin and other fluoroquinolones. An MOS Hypersil (C8) reversed-phase column (5 pm, 15 cm x 4.6 mm) was used with UV detection at 280 nm. The mobile phase was tetrahydrofuran-acetonitrile-H3PC>4 (10 mM)-triethylamine (10 30 60 0.03 by volume) with a flow rate of 1.5 mL/min. 

Ross, D.L. and Riley, C.M. Physicochemical properties of the fluoroquinolone antimicrobials III. Complexation of lomefloxacin with various metal ions and the effect of metal complexation on aqueous solubility. Int. J. Pharm.,... 

Trimethoprim is the only weak base listed (fluoroquinolones and sulfonamides are acidic compounds), and its high lipid solubility at blood pH allows penetration of the drug into prostatic and vaginal fluid to reach levels similar to those in plasma. Leukopenia and thrombocytopenia may occur in folate deficiency when the drug is used alone or in combination with sulfamethoxazole. Fluoroquinolones do not exacerbate symptoms of folic acid deficiency. The answer is (D). 

As was used in much of our earlier work on incorporation of antibiotic into existing polyester substrates, Cipro was the antibiotic chosen for this study. Antibiotics vary m structural type, spectrum of activity, and clinical usefidness. Cipro is one of the fluoroquinolones, a family of more than ten antibiotics and the drug of choice for many applications" . Quinolone antibiotics are chemically stable, and effective at low concentrations against the common clinically encountered organisms, particularly those bacteria responsible for biomaterial infection". These antibiotics also have structural features (solubility, molecular mass, and functional groups) that coincide with those of textile dyes and our previous wodc has shown that these similarities lead to the potential for dye-like interactions with polymeric materials " . 

Quinolones, especially fluoroquinolones such as ciprofloxacin and ofloxacin, have been detected in wastewater, sludge, and surface water [147,154,158,159]. Quinolones have amphoteric and zwitterionic characters with pKa cooH = 5.9 — 6.3 and pfCa NH2 = 7.9 — 10.2 [158]. Between the values of pH 6 and 8, they exhibit poor water solubility as... 

Due to the presence of the carboxyl and fi-oxo groups, as well as azaheterocyclic fragments, fluoroquinolones have a profound ability to form metal-chelates, and other ionic structures. It is known that complexes with metals may enhance activity of fluoroquinolones due to a better solubility and endocellular accumulation [357, 358]. The crystal structures of a number of metal complexes, results of their thermal analysis, IR and NMR spectra of complexes and their bioactivity have been considered [359]. In the recently published review article [360] the data concerning the structure and properties of metal complexes of fluoroquinolones, and their interaction... 

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