Tetracyclines elimination

At present oral doses, tetracycline and its derivatives produce mild hepatic steatosis in humans at worst. However, fatal cases of microvesicular steatosis have occurred in the past, usually after 4—10 days of intravenous administration of high doses of either tetracycline or diverse tetracycline derivatives (Zimmerman 1978). Predisposing conditions (Zimmerman 1978) included preexisting renal failure, which decreases tetracycline elimination, or pregnancy, which can impair mitochondrial function. 

Cholera is a serious infection causing epidemics throughout Asia. Although a toxin-mediated disease, largely controlled with replacement of fluid and electrolyte losses, tetracycline has proved effective in eliminating the causative vibrio from the bowel, thereby abbreviating the course of the illness and reducing the total fluid and electrolyte losses. 

M. B., Tanya, V.N., Donnely, M.J. and Trees, A.J. (2000) Macrofilaricidal activity of tetracycline against the filarial nematode Onchocerca ochengi elimination of Wolbachia precedes worm death and suggests a dependent relationship. Proceedings of the Royal Society of London B 267, 1063-1069. 

The elimination half-life of which of the following tetracyclines remains unchanged when the drug is administered to an anuric patient ... 

Biodegradation occur either in aerobic or in anaerobic conditions, and as detailed below, it is the most important elimination process in WWTPs. This is an important degradation process for diclofenac, ofloxacin (OFLO), sulfamethoxazole and tetracyclines (TCs) [40]. Several fungi, such as Mucor ramannianus, present in soils, aheady have been shown to metabolize FQs [41]. 

Tomato canker caused by Xanthomonas can be controlled by the application of tetracycline(52-53). Streptomycin resistant strains of bacteria have Been found on peach, tomato and peppers(54), and the mixture of two antibiotics has helped to stop tHe build-up of resistance in the patho -gens in some cases(55-56). The silvery disease of sugar-beet caused by Coryn 5actferium is insufficiently controlled by mercurial compounds, but is completely eliminated when seeds are dipped for several hours in a solution of streptomycin. 

Two tetracyclines have sufficiently distinctive features to warrant separate mention. Doxycycline, with its longer half-hfe and lack of nephrotoxicity, is a popular choice for patients with preexisting renal disease or those who are at risk for developing renal insufficiency. The lack of nephrotoxicity is related mainly to biliary excretion, which is the primary route of doxycycline elimination. Doxycycline is the preferred parenteral tetracycline Doxycycline is a potential first-hne agent in the prophylaxis of anthrax after exposure. Doxycycline is the treatment of choice for the primary stage of Lyme disease in adults and children older than 8 years. 

Atovaquone is poorly absorbed from the gastrointestinal tract, but absorption is increased with a fatty meal. Excretion of the drug, mostly unchanged, occurs in the feces. The elimination half-life is 2 to 3 days. Low plasma levels persist for several weeks. Concurrent administration of metoclopramide, tetracycline, or rifampin reduces atovaquone plasma levels by 40 to 50%. 

By definition, the fraction that enters the circulatory system is eliminated by extrarenal mechanisms (usually metabolism by the liver and other tissues) and is derived by the difference from renal excretion that is, 1 — Fg. The excretory organs are able to eliminate polar compounds such as tetracycline and tylosin more efficiently than compounds that are highly soluble in lipids (i.e., lipophilic) such as metronidazole, erythromycin, clindamycin, and trimethoporin. Thus, the highly lipophilic compounds will not be eliminated until they are metabolized to more polar intermediates. 

Tetracyclines mainly differ in their absorption after oral administration and their elimination. Absorption after oral administration is approximately 30% for chlortetracycline 60-70% for tetracycline, oxytetracycline, demeclocycline, and methacycline and 95-100% for doxycycline and minocycline. Tigecycline is poorly absorbed orally and must be administered intravenously. A portion of an orally administered dose of tetracycline remains in the gut lumen, modifies intestinal flora, and is excreted in the feces. Absorption occurs mainly in the upper small intestine and is impaired by food (except doxycycline and... 

Tetracyclines are excreted mainly in bile and urine. Concentrations in bile exceed those in serum tenfold. Some of the drug excreted in bile is reabsorbed from the intestine (enterohepatic circulation) and may contribute to maintenance of serum levels. Ten to 50 percent of various tetracyclines is excreted into the urine, mainly by glomerular filtration. Ten to 40 percent of the drug is excreted in feces. Doxycycline and tigecycline, in contrast to other tetracyclines, are eliminated by nonrenal mechanisms, do not accumulate significantly and require no dosage adjustment in renal failure. 

Deprotection and oxidation of 12 gave 13, which was further oxidized to the sulfoxide. Elimination of the sulfoxide gave the naphthalene derivative 14, which underwent spontaneous oxidation to 15. Reductive deprotection then gave tetracycline 16. The diastereoselectivity of the air and light-mediated oxidation is remarkable. 

Some of the administered dosage is concentrated in liver, excreted in bile, and reabsorbed from the intestines so that a small amount may persist in the blood for a long time after administration, due to enterohepatic circulation. The persistence of tetracyclines in the blood following absorption is a surprising contrast to other antibiotics that are eliminated more rapidly. Some absorption of tetracyclines into the bloodstream may also occur following intramammary infusion. 

They undergo minimal or no metabolism and they are excreted in urine and feces either unchanged or in a microbiologically inactive form. Although there have been differences among individual tetracyclines as to their urinary and fecal excretion, these differences are not substantial. Tetracyclines are also eliminated in milk (233), attaining approximately 50-60% of the plasma concen-... 

Strong crossreactivity to chlortetracycline has been also observed when a commercialized kit (70) was applied to analyze tetracycline, chlortetracycline, and oxytetracycline residues in honey (71). The detection limit for both tetracycline and chlortetracycline was at 15 ppb, but for oxytetracycline at 250 ppb due to the low crossreactivity of the used antibodies to this analyte. Experiments using honey free of tetracyclines showed that dilution of honey with buffer at a ratio of a 1 50 was sufficient to eliminate matrix interferences. 

Elimination of coextracted materials and concentration of tetracyclines have also been accomplished using mixed-phase extraction membranes with both re-versed-phase and cation-exchange properties (294,295), or solid-phase extraction columns packed with cation-exchange materials such as CM-Sephadex C-25 (301), aromatic sulfonic acid (310), and carboxylic acid (283, 300). For the same purpose, metal chelate affinity chromatography has also been employed. In this technique, the tetracyclines are specifically absorbed on the column sorbent by chelation with copper ions bound to small chelating Sepharose fast flow column (278-281, 294-296). 

Note The main objective in the clinical management of patients suffering from an acute malaria attack is the prompt elimination of the parasite form responsible for the symptoms, that is, the asexual erythrocytic form. Drugs that are particularly effective in this regard are called schizontocidal or suppressive agents. They include such compounds as amodiaquine, chloroguanide, chloroquine, hydroxychloroquine, pyrimethamine, quinine, and tetracycline. 

Hepatic dysfunction Antibiotics that are concentrated or eliminated by the liver (for example, erythromycin, tetracycline) are contraindicated in treating patients with liver disease. 

Age Renal or hepatic elimination processes are often poorly developed in newborns, making neonates particularly vulnerable to the toxic effects of chloramphenicol (see p. 320) and sulfonamides (see p. 289). Young children should not be treated with tetracyclines (see p. 311) which affect bone growth, or fluoroquinolones (see p. 323), which interfere with cartilage growth. 

When cells are transformed with naked vector DNA (as opposed to packaged, protein associated DNA in viruses) only a fraction of the cells, 10% under the best conditions, take up the DNA. Therefore, the cells receiving the DNA or the Transformants have to be isolated from among the non-receiving Tmtransformed cells. This is accomplished by using the selectable property encoded by the vector, such as resistance to antibiotics (ampicillin, tetracycline, etc.). Exposure of the mixed population of transformed and untransformed cells to the antibiotic results in the elimination of untransformed cells. Transformed bacterial cells can be isolated, grown, and vector DNA prepared from them for introduction into the expression host cell of choice. 

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