Absorption, antimicrobial drugs

Although theoretically safe, poorly absorbed antimicrobials could become absorbable in the presence of mucosal inflammatory or ulcerative changes [100], like those occurring in IBD or when invasive bacteria colonize the intestine. To verify whether the presence of intestinal lesions would affect rifaximin absorption, the drug was given to rats with experimentally induced colitis [101]. The indomethacin-induced enteropathy did not affect intestinal absorption of rifaximin. However, under the same experimental conditions, systemic bioavailability of neomycin did increase [101]. 

Hilgers AR, Smith DP, Biermacher JJ, Day JS, Jensen JL, Sims SM, Adams WJ, Friis JM, Palandra J, Hosley JD, Shobe EM, Burton PS (2003) Predicting oral absorption of drugs A case study with a novel class of antimicrobial agents. Pharm. Res. 20 1149-1155. 

From an in vitro perspective, solubility in water and in organic solvents determines the choice of solvent, which, in turn, influences the choice of extraction procedure and analytical method. Solubility can also indirecfly impact the timeframe of an assay for compounds that are unstable in solution. From an in vivo perspective, the solubility of a compound influences its absorption, distribution, metabolism, and excretion. Both water solubility and lipid solubility are necessary for the absorption of orally administered antimicrobial drugs from the gastrointestinal tract. This is an important consideration when selecting a pharmaceutical salt during formulation development. Lipid solubility is necessary for passive diffusion of drugs in the distributive phase, whereas water solubility is critical for the excretion of antimicrobial drugs and/or their metabolites by the kidneys. 

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... 

The IM and SC routes are by far the most frequently used extravascular parenteral routes of drug administration in farm animals. The less frequently used parenteral routes have limited application, in that they aim at directly placing high concentrations of antimicrobial agent close to the site of infection. These routes of administration include intra-articular or subconjuctival injection and intra-mammary or intra-uterine infusion. These local routes differ from the major parenteral routes in that absorption into the systemic circulation is not a prerequisite for delivery of drug to the site of action. The combined use of systemic and local delivery of drug to the site of infection represents the optimum approach to... 

This drug exceeds lincomycin in all positive respects, including absorption into the gastrointestinal tract, antibacterial activity, and antimicrobial spectmm. Synonyms of this drag are cleocin, clinimycin, dalacin, and others. 

Metabolism The sulfas are acetylated at N4, primarily in the liver. The product is devoid of antimicrobial activity, but it retains the toxic potential to precipitate at neutral or acidic pH, causing crys-talluria ( stone formation ) and therefore potential damage to the kidney (Figure 29.4). Sulfasalazine is effective in the treatment of inflammatory bowel disease because local intestinal flora split the drug into sulfapyridine and 5-aminosalicylate. The latter exerts the antiinflammatory effect. Absorption of sulfapyridine can lead to toxicity in patients who are slow acetylators. 

The potential effects of packaging component/dosage form interactions are numerous. Hemolytic effects may result from a decrease in tonicity and pyrogenic effects may result from the presence of impurities. The potency of the drug product or concentration of the antimicrobial preservatives may decrease due to adsorption or absorption. 

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