Ciprofloxacin chelation

Absorption of antimicrobial agents such as fluoroquinolones and tetracyclines that can be bound by divalent and trivalent cations potentially could be compromised by administration with EN formulas containing these cations. The fluoroquinolones (e.g., levofloxacin and ciprofloxacin) have been best studied in this regard, and results of studies are not consistent. Mechanisms for an interaction between fluoroquinolones and EN formulas other than chelation by cations have been postulated.40 Some institutions hold tube feedings for 30 to 60 minutes or more before and after enteral dosages of fluoroquinolones. Because ciprofloxacin absorption has been shown to be decreased with jejunal administration, this drug probably should not be given by jejunal tube.41... 

All quinolones interact with multivalent cations, forming chelation complexes resulting in reduced absorption. Major offenders are antacids vitamins containing calcium and iron can also be problematic. All fluoroquinolones interact with warfarin, didanosine (ddi), and phenytoin, resulting in decreased absorption or metabolism. Ciprofloxacin and other second-generation drugs interact with theophylline by decreasing its clearance, which leads to theophylline toxicity. 

QUINOLONES DIDANOSINE 1 efficacy of ciprofloxacin and possibly levofloxacin, moxifloxacin, norfloxacin and ofloxacin with buffered didanosine Cations in the buffer of didanosine preparation chelate and adsorb ciprofloxacin. Absorption of the other quinolones may be i by the buffered didanosine formulation, which raises gastric pH Give the antibiotic 2 hours before or 6 hours after didanosine. Alternatively, consider using the enteric-coated formulation of didanosine, which does not have to be given separately... 

CIPROFLOXACIN, NORFLOXACIN DAIRY PRODUCTS 1 norfloxacin levels, with risk of therapeutic failure The calcium from dairy products is thought to form an insoluble chelate with norfloxacin, leading to 1 absorption from the gut Dairy products should be avoided for 1-2 hours before and after taking norfloxacin. Alternatively, moxifloxacin, enoxacin, lomefloxacin and ofloxacin can be used as alternative therapies as they show minimal interaction... 

Milk and dairy foods decrease the absorption of some tetracyclines (doxycycline and minocycline are not affected), some quinolone antibiotics (absorption of ciprofloxacin and norfloxacin is decreased but ofloxacin is not affected), penicillamine and alendronate. Large volumes of milk can reduce the ulcer-healing properties of bismuth tripotassium dicitratobismuthate (bismuth chelate),... 

CALCIUM ANTIBIOTICS -QUINOLONES (CIPROFLOXACIN) TETRACYCLINES 1 antibiotic levels 1 absorption due to formation of unabsorbable chelates Separate doses by at least 2 hours... 

Dandelion 2. Fennel 3. Guar gum 4. Khat 5. Yohimbine 1. Ciprofloxacin 2. Amoxicillin 3. Penicillin 4. Tetracycline 1 blood levels may potentially 1 antibacterial potential Unknown mechanism (dandelion 1 ciprofloxacin levels in rats khat 1 absorption and thus blood levels of ampicillin and amoxicillin, possibly due to the formation of a tannin-antibiotic complex guar gum 1 absorption of penicillin) Other mechanism (yohimbine chelates tetracyclines). Fennel extracts are considered to chelate with ciprofloxacin Be aware. Discontinue the herb during the course of antibiotic therapy. Penicillins should be taken on an empty stomach... 

Bind to other drugs that are administered within 1 or 2 hours of the antacid, This process results in reduced availability of the co-administered drug for absorption, For example, the chelation of tetracyclines (e.g, tetracycline, doxycycline) will decrease their absorption by up to 90%, Avery similar process - precipitation - occurs with drugs such as quinine with aluminium and magnesium hydroxide preparations, which results in a decreased absorption of quinine, It has to be noted that the absorption of fluoroquinolones (e g. ciprofloxacin, norfloxacin, ofloxacin, enoxacin, perfloxacin i will be decreased by 60-75% if they are co-administered with divalent and trivalent cations. Patients are recommended not to take these divalent and trivalent cationic preparations until fluoroquinolone therapy is discontinued. 

Interactions. Iron chelates in the gut with tetracyclines, penicillamine, methyldopa, levodopa, carbidopa, ciprofloxacin, norfloxacin and ofloxacin it also forms stable complexes with thyroxine, captopril and biphosphonates. These interactions can be clinically important. Ingestion should be separated by 3 hours. 

Chelation of ciprofloxacin (V) by aluminium hydroxide and calcium carbonate reduces bioavailability, as seen in Fig. 10.11. Other quinolones (VI-IX), undoubtedly suffer the same fate. 

Other mechanism (yohimbine chelates tetracyclines). Fennel extracts are considered to chelate with ciprofloxacin... 

The proposed reason for these changes is that the calcium in milk and yoghurt or other dairy products combines with the ciprofloxacin and norfloxacin to produce insoluble chelates. Compare also Quinolones -i-Antacids or Calcium compounds , p.328. 

Didanosine is extremely acid labile at pH values below 3, so one ofthe formulations contains buffering agents (dihydroxyaluminium sodium carbonate and magnesium hydroxide) to keep the pH as high as possible to minimise the acid-induced hydrolysis. Ciprofloxacin forms insoluble non-absorbable chelates with these metallic ions in the buffer so that its bioavailability is markedly reduced. See also Quinolones + Antacids or Calcium compounds , p.328. 

It has also been suggested that alteration in pH as well as the presence of cations are required to form chelates with ciprofloxacin and while this helps explain the lack of effect of high calcium in a high fat breakfast, it does not explain the significant effect with enteral feeds or calcium-fortified orange juice. The differences seen in men and women are possibly due to a slower gastric emptying rate in men, which increases the exposure of the quinolone to the enteral feed. ... 

It is believed that the quinolones form a complex with iron and zinc (by chelation between the metal ion and the 4-oxo and adjacent carboxyl groups), which is less easily absorbed by the gut. However, a study in rats using oral iron and intravenous ciprofloxacin suggested that the interaction may not be entirely confined to the gut. This needs further study. Iron-ovotransferrin differs from other iron preparations in being able to combine directly with the transferrin receptors of intestinal cells, and appears to release little iron into the gut to interact with the quinolones. 

The determination of amoxicilline, ciprofloxacin, and piroxicam in bulk and pharmaceutical preparations has been performed by combining the oxidation character of Fe(III) with the chelation property of Fe(II), affording highly colored complexes. The reagent solutions are (1) a mixture of 1,10-phenanthroline and iron(III) ammonium sulfate in hydrochloride medium and (2) 2,2 -bipyridyl and iron(III) ammonium sulfate in hydrochloride medium. The resulting Fe(II) concentration, proportional to the amount of drug present, is monitored by the measurement of absorbances of tris(o-phenanthro-line) iron(U) or tris (bipyridyl) iron(II) complexes at 510 and 522 nm, respectively. 

An active substance, although initially released from its dosage form (and dissolved), may become unavailable for absorption due to reactimis with other medicines or food components [4]. An example is the formation of insoluble complexes of tetracycline with calcium or aluminium ions from antacids or milk products. Interaction (chelation or binding) with iron ions leads to a reduced absorption for a variety of active substances such as doxycycline, penicillamine, methyldopa and ciprofloxacin. The absorption of active substances showing pH-dependent dissolution behaviour may be influenced by medicines that influence the gastric pH, such as H2-antagonists, proton pump inhibitors and antacids. Antimycotic active substances such as ketoconazole or itraconazole dissolve better in acidic fluids. Therefore their bioavailability may be increased by the concomitant use of an acidic drink like cola, whereas the concomitant use of antacids or proton pump inhibitors is likely to reduce the bioavailability. Concomitant use of milk may increase the dissolution of acidic active substances, whereas fats from food may increase the bioavailability of lipophilic active substances like albendazole and griseofulvin. 

Drag-drag interactions can be a physical (e.g., changing the pH, which depends on the absorption of these compounds as ketoconazole and glipizide), chemical (e.g., ciprofloxacin is a chelator of cations such as aluminum, magnesium and iron), and biological, which depends on interactions with human proteins. The last type of interaction is of great interest for computational predictions. 

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