Fluoroquinolones bioavailability

We then used this Caco-2 cell assay to categorize representative fluoroquinolone drug substance permeability [50], The drugs demonstrated some concentration-dependent permeability indicative of active drug transport. Based upon comparison to labetalol, ciprofloxacin was classified as a LP drug, whereas levofloxacin, lomefloxacin, and ofloxacin were classified as HP drugs, which matched their human in vivo bioavailabilities. All four fluoroquinolone drugs were subject to efflux transport (ciprofloxacin > lomefloxacin > rhodamine 123 > levofloxacin > ofloxacin). 

In terms of pharmacokinetics, LVX has an excellent profile. With an oral dose of 500 mg, LVX has a bioavailability of >99%, an AUC range of 41.9-47.7 mgh/mL, Cmax of 4.5-6.2 mg/mL, a clearance of 10.5-11.9 L/h, and a volume of distribution (Vd) of 1.3 L/kg (Hurst et al., 2002). In terms of protein bound material, only 24-38% is affected (Fish, 2003). Like other fluoroquinolones, there is a 19-44% AUC reduction when co-administered with an aluminum or magnesium antacid or iron sulfate (Qaqish and Polk, 2003). The major metabolite of levofloxacin arises from glucuronidation (Brysk-ier, 2005). 

Compounds in which the presence of fluorine atoms enhances the efficiency and selectivity of the biological activity with respect to the nonfluorinated parent compounds. These fluorocompounds should have fewer unfavorable effects. Due to these features (safety of use, better bioavailability, reduced dose, minor toxicity, etc.), these compounds have replaced, sometimes entirely, the nonfluorinated compounds of the same class. Volatile anesthetics and fluoroquinolones can be cited as examples of this category. 

After oral adrninistration, the fluoroquinolones are well absorbed with the bioavailability of 80 to 95 % and distributed widely in body fluids and tissues. Depending upon the newer compound, the different dose regimen have been adopted. The fluoroquinolones are excreted mainly by tubular secretion and by glomerular filtration. 

It is the levoisomer of ofloxacin and having better activity than ciprofloxacin and ofloxacin against S. pneumoniae. It is also used in chronic bronchitis, sinusitis, pyelonephritis, and other related infections of soft tissues. Due to high oral bioavailability, patient can be shifted from IV to oral therapy. It can be administered just once a day regimen as an alternate to other fluoroquinolones in the treatment of respiratory infections. 

As a rule, when quinolones are administered orally, their absorption from the gastrointestinal tract is rapid and almost complete, but food in the stomach delays their absorption. In unweaned calves, fluoroquinolones are often given in the milk replacer, but oral bioavailability is slightly reduced compared with the oral drench (139). On tire other hand, fermentation in the rumen of mature ruminants precludes the oral use of fluoroquinolones. Injectable solutions are also available for systemic therapy of large animals and turkeys. 

The coadministration of mycophenolate mofetil with antacids results in decreased absorption. The plasma MPA concentration is significantly reduced by cholestyramine due to binding of the cholestyramine to MPAG in the intestine and interfering with the enterohepatic recirculation of the drug. The bioavailability of mycophenolate mofetil is higher when administered with tacrolimus as opposed to cyclosporine. The bioavailability of MPA is reduced by antibiotics including fluoroquinolones and metronidazole. 

Absorption Only 35-70% of oral norfloxacin is absorbed. However, 70-90% of the other fluoroquinolones are absorbed after oral administration. Bioavailability is greatest for ofloxacin and lomefloxacin. Intravenous preparations of ciprofloxacin and ofloxacin are available. Ingestion of the fluoroquinolones with sucralfate, antacids containing aluminum or magnesium, or dietary supplements containing iron or zinc can interfere with the absorption of these antibacterial agents. 

The maximum plasma concentration reflects the extent of drug bioavailability. It can be used in relation to minimum inhibitory concentration (MIC) to predict the efficacy of concentration-dependent antimicrobial agents (e.g. fluoroquinolones, aminoglycosides). Both the maximum (peak) and minimum (trough) plasma concentrations are used during therapeutic drug monitoring to maximize efficacy and minimize the occurrence of undesirable effects. 

Absorption can be affected by the presence of an efflux mechanism such as P-glycoprotein. Drug binding may affect oral absorption fluoroquinolones bind to cations and form insoluble chelates, resulting in a decrease of bioavailability (11). 

May cause mild CNS and GI effects and 1 bioavailability of drugs that require acidity for oral absorption (e.g., fluoroquinolones, ketoconazole). Inhibit P450 — >L elimination of diazepam, phenytoin, and warfarin. 

Despite the fact that a plethora of dietary factors could, and will, affect the absorption characteristics of phytochemicals, this area has not been systematically explored. One reason might be the complexity of dietary factors and their interactions that could affect absorption. A nonexhaustive list would include the volume and composition of the food consumed, pH, caloric density, viscosity, nutrients (carbohydrates, protein, fat, fibers), alcohol, caffeine, and the presence of other phytochemicals. Such dietary factors affect the functional status, motility, and acidity of the gastrointestinal tract in a complex manner and modify the physicochemical properties, formulation, and dissolution characteristics of the compound of interest. Calcium in dairy products, for example, has the potential to chelate tetracyclines and fluoroquinolones and, thereby, reduce their bioavailability and biological activity [31]. 

Stass H, Kubitza D. Effects of iron siqiplements on the oral bioavailability of moxifloxacin, a novel 8-m ethoxy fluoroquinolone, inhumans. ClinPharmacolanet(2QO ) 40 (Suppl 1), 57-62. 

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