Doxycycline excretion

Craig N K Jaffe JM, Colaizzi JL and Foust RI, Effect of altered urinary pH on tetracycline and doxycycline excretion in humans, J. Pharmacokinet. Biopharm., 1, 267-282 (1973). 

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... 

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. 

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. 

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. 

Fate All the tetracyclines concentrate in the liver, where they are, in part, metabolized and conjugated to form soluble glucuronides. The parent drug and/or its metabolites are secreted into the bile most tetracyclines are reabsorbed in the intestine and enter the urine by glomerular filtration. Doxycycline is an exception, since its metabolite is preferentially excreted via the bile into the feces. Thus, unlike other tetracyclines, doxycycline can be employed in treating infections in renally compromised patients. 

All tetracyclines are excreted in the urine and faeces. The primary route for most is the kidney (by glomerular filtration). Doxycycline is excreted in the faeces as an... 

Pharmacokinetics. Most tetracyclines are only partially absorbed from the alimentary tract, enough remaining in the intestine to alter the flora and cause diarrhoea. They are distributed throughout the body and cross the placenta. Tetracyclines in general are excreted mainly unchanged in the urine and should be avoided when renal function is severely impaired. Exceptionally, doxycycline and minocycline are eliminated by nonrenal routes and are preferred for patients with impaired renal function. 

Doxycycline is well absorbed from the gut, even after food. It is excreted in the bile, in the faeces which it re-enters by diffusing across the small intestinal wall and, to some extent, in the urine (t y 16 h). These nonrenal mechanisms compensate effectively when renal function is impaired and no reduction of dose is necessary 200 mg is given on the first day, then 100 mg/d. 

In another study, a 16-week, randomized, double-blind, placebo-controlled trial, eligible subjects with active seropositive or erosive rheumatoid arthritis were randomly allocated to three treatment groups doxycycline 200 mg intravenously, azithromycin 250 mg orally, or placebo (24). The primary end-points were changes between baseline and week 4 in the tender joint count, erythrocyte sedimentation rate, and urinary excretion of pyridinoline. The trial was stopped prematurely after 31 patients had been enrolled. Three subjects were withdrawn because of worsening arthritis. There were no significant differences across the groups in any of the three primary clinical endpoints. The authors concluded that doxycycline did not reduce disease activity or collagen cross-link production. 

Elimination Tetracycline and minocycline are excreted mainly in bile and urine. Doxycycline is eliminated by nonrenal mechanisms. Doxycycline is the tetracycline of choice in patients with renal insufficiency. T /i doxycycline = minocycline > tetracycline. 

The lipid solubility of four tetracyclines (minocycline, doxycycline, tetracycline and oxytetracycline) correlates inversely with the mean concentration of antibiotic in plasma and with renal uptake and excretion. Only the more lipophilic minocycline and doxycycline pass across the blood-brain and blood-ocular barriers in detectable concentrations. Table 5.19 gives some of these characteristics of the tetracyclines. These analogues of tetracycline, while active in vitro against meningococci, are... 

Tetracycline was discovered after a team of workers examined 100000 soil samples from around the world. Tetracycline derivatives include chlor-tetracycline, oxytetracycline, doxycycline and minocycline. The tetracyclines have a broad spectrum of activity they are effective against Grampositive and Gram-negative bacteria, some anaerobes. Chlamydia, Mycoplasma, Ehrlichia and Rickettsia spp. and some protozoa. Their activity against staphylococci is usually limited and they are not active against enterococci. E. coli, Klebsiella, Proteus and Pseudomonas spp. are usually resistant. Doxycycline and minocycline are usually more active in vitro than the other tetracyclines. Differences in the clinical efficacy of the tetracyclines can be attributed to differences in the absorption, distribution and excretion of the individual drugs rather than to differences in bacterial susceptibility. 

The tetracyclines, apart from doxycycline and minocycline, are slowly eliminated by renal excretion (glomerular filtration). Their slow elimination can be attributed to enterohepatic circulation whereby drug excreted by the liver in bile is reabsorbed from the intestine. The half-life of oxytetracycline differs widely between animal species goat (3.4 h), cattle (4.0 h), sheep (5.2 h), dog (6.0 h), pig (6.0 h), donkey (6.5 h), horse (9.6 h), and red-necked wallaby (.Macropus rufogriseus) (11.4 h). Doxycycline, unlike other tetracyclines, is eliminated by biliary excretion and diffusion into the intestine. The half-life of doxycycline is relatively short in dogs (7.0 h) and cats (4.6 h) compared with human beings (16 h). The half-life of doxycycline in chickens (4.8 h) is shorter than in turkeys (10 h) (Santos et al, 1996). Minocycline is mainly eliminated by hepatic metabolism. 

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