Tetracycline excretion

KOning A, Muhlbauer RC, Fleisch H (1988) Tumor necrosis factor alpha and interleukin-1 stimulate bone resorption in vivo as measured by urinary [3H]tetracycline excretion from prelabeled mice. J Bone Miner Res 3 621-627... 

As indicated, the ionized form of a drug will be more soluble than the nonionized form in the aqueous fluids of the GIT. The classic studies on the beneficial effects of changing nonionized drugs into salt forms were reported by Nelson for tetracycline [25], and Nelson et al. for tolbutamide [26]. Table 2 combines portions of the data from each study. Urinary excretion of the drug or its metabolite was taken as the in vivo measure of the relative absorption rate for the salt and the nonionized... 

The most important evidence is probably offered by a recent double-blind, randomized trial which showed a better therapeutic effect of rifaximin in comparison to tetracycline in a cohort of SIBO syndrome patients [42] in particular, rifaximin administration produced a significant reduction of breath hydrogen levels in fasting conditions, peak of hydrogen excretion and cumulative breath hydrogen excretion after an oral dose of 50 g of glucose (fig. 1). Normalization of the test results was evident in 70% of the sample studied. 

BUN) levels This is of clinical importance in patients with impaired renal function. With the exception of cl oxycy cline, tetracyclines should not be used in patients that are anuric. Doxycycline is excreted by the G1 tract under these conditions, and it will not accumulate in the serum of patients with renal insufficiency... 

Organisms may be considered susceptible if the Minimum Inhibitory Concentration (MIC) is not more than 4.0 yg/ml and intermediate if the MIC is 4.0-12.5 yg/ml (see Table 1). Tetracyclines are readily absorbed and are bound to plasma proteins in varying degrees. They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations and in a biologically active form. 

The effects of tetracycline injection following injection of thorium-228 were not reported. Studies with a similar actinide element, plutonium, suggest that a thorium-tetracycline complex may be formed, which is excreted rapidly through the kidneys. Similarly, chelating agents such as EDTA... 

Differences in clinical effectiveness are partly due to differences in absorption, distribution and excretion of the individual drugs. In general tetracyclines are absorbed irregularly from the gastrointestinal tract and part of the dose remains in the gut and is excreted in the faeces. However this part is able to modify the intestinal flora. Absorption of the more lipophilic tetracyclines, doxycycline and minocycline is higher and can reach 90-100%. The absorption is located in the upper small intestine and is better in the absence of food. Absorption is impaired by chelation with divalent cations. In blood 40-80% of tetracyclines is protein bound. Minocycline reaches very high concentrations in tears and saliva. Tetracyclines are excreted unchanged, in both the urine by passive filtration and in the feces. Tetracyclines are concentrated in the bile via an active... 

The tetracyclines are metabolized in the liver and are concentrated in the bile. Bile concentrations can be up to five times those of the plasma. Doxycycline, minocycline, and chlortetracycline are excreted prima-... 

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. 

Mechanism of Action A tetracycline antibacterial that inhibits bacterial protein synthesis by binding to ribosomal receptor sites also inhibits ADH-induced water reabsorption. Therapeutic Effect Bacteriostatic also produces water diuresis. Pharmacokinetics Food and dairy products interfere with absorption. Protein binding 41 %-91%. Metabolized in liver. Excreted in urine. Removed by hemodialysis. Half-life 10-15 hr. 

Certain drugs are excreted in urine only in small amounts but appear in high concentrations in the bile for example, erythromycin, novobiocin, tetracycline, phenolphthalein etc. The abnormality or any disease related to liver may impair bile secretion which can lead to the accumulation of certain drugs like probenecid, digoxin etc. This can also lead to decreased drug metabolism and decreased rates of secretion of drugs into bile. 

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. 

Tetracyclines are classified as short-acting (chlortetracycline, tetracycline, oxytetracycline), intermediate-acting (demeclocycline and methacycline), or long-acting (doxycycline and minocycline) based on serum half-lives of 6-8 hours, 12 hours, and 16-18 hours, respectively. Tigecycline has a half-life of 36 hours. The almost complete absorption and slow excretion of doxycycline and minocycline allow for once-daily dosing. 

The oral dosage for rapidly excreted tetracyclines, equivalent to tetracycline hydrochloride, is 0.25-0.5 g four times daily for adults and 20-40 mg/kg/d for children (8 years of age and older). For severe systemic infections, the higher dosage is indicated, at least for the first few days. The daily dose is 600 mg for demeclocycline or methacycline, 100 mg once or twice daily for doxycycline, and 100 mg twice daily for minocycline. Doxycycline is the oral tetracycline of choice because it can be given as a once-daily dose and its absorption is not significantly affected by food. All tetracyclines chelate with metals, and none should be orally administered with milk, antacids, or ferrous sulfate. To avoid deposition in growing bones or teeth, tetracyclines should be avoided in pregnant women and children less than 8 years of age. 

Two bismuth compounds are available bismuth subsalicylate, a nonprescription formulation containing bismuth and salicylate, and bismuth subcitrate potassium. In the USA, bismuth subcitrate is available only as a combination prescription product that also contains metronidazole and tetracycline for the treatment of H pylori. Bismuth subsalicylate undergoes rapid dissociation within the stomach, allowing absorption of salicylate. Over 99% of the bismuth appears in the stool. Although minimal (< 1%), bismuth is absorbed it is stored in many tissues and has slow renal excretion. Salicylate (like aspirin) is readily absorbed and excreted in the urine. 

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-... 

Chlortetracycline has, in many respects, a pharmacological profile similar to that of oxytetracycline. Similarly to other tetracyclines, the main excretory routes are through the urinary system, biliary system, and intestine. Its higher biliary excretion rate makes chlortetracycline a better choice than oxytetracycline for liver infections. 

Doxycycline tends to be more active against some bacteria than other tetracyclines. This is probably due to its slower excretion rather than to enhanced oral absorption. Doxycycline is used in cases where cost is unimportant. It is a very lipophilic drug that shows a high bioavailability, being almost completely absorbed after oral administration to different animal species except chickens (250, 251). 

After oral administration, doxycycline is rapidly and well absorbed from the gastrointestinal tract. It has a half-life of 15-22 h, which is longer than that of other tetracyclines. Following administration by various routes, doxycycline is widely distributed in the body, with highest levels in kidney and liver, besides bones and dentine. Doxycycline may be metabolized for up to 40%, and is largely excreted in feces via bile and intestinal secretion. 

The three tetracyclines most recently marketed were made by a semisynthetic pathway. The first of these were methacycline (6-methylene oxytetracycline) (5), C22H22N2OS. and its reduction product doxycycline (6). C22H24CIN2O2- The latter compound is a potent antibiotic which is well-absorbed and slowly excreted, thus allowing small and infrequent (once or twice a day) dosage schedules. Finally, the most recent addition to the commercial tetracyclines is minocycline (7). C21H27N3O7. which is also well-absorbed and slowly excreted. 

---