Minocycline excretion

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-... 

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 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. 

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. 

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. 

Minocycline differs from other tetracyclines in that its antibacterial spectrum includes Neisseria meningitidis and it has been used for meningococcal prophylaxis. It is well absorbed from the gut, even after a meal, partly metabolised in the liver and partly excreted in the bile and urine (t/ 15 h). Dose reduction is not necessary when renal function is impaired 200 mg initially is followed by 100 mg 12-hourly. Minocycline but not other tetracyclines may cause a reversible vestibular disturbance with dizziness, tinnitus and impaired balance, especially in women. 

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. 

The absorption of tetracyclines from the G1 tract is non-uniform. Up to 30% of chlortetracycline is absorbed. The absorption for tetracycline, oxytetracycline, and demeclo-cycline ranges between 60 and 80%, whereas as much as 90 to 100% of doxycycline and minocycline is absorbed. The absorption of tetracyclines is impaired by divalent cations (calcium, magnesium, and ferrous iron), by aluminum, and by extremely alkaline pHs. Tetracyclines are distributed widely throughout the body fluid, cross the placental barrier, and can accumulate in growing bones. The concentrations of chlortetracycline in spinal fluid are only one fourth of those in plasma. Minocycline, a more lipid-soluble tetracycline, reaches a high concentration in tears and saliva and can eradicate the meningococcal carrier state. The tetracyclines are metabolized in the liver and excreted mainly by the bile and urine. The concentrations of tetracyclines in the bile are ten times higher than those in serum. 

B. Pharmacokinetics Oral absorption is variable, especially for the older drugs, and may be impaired by foods and multivalent cations (calcium, iron, aluminum). Tetracyclines have a wide tissue distribution and cross the placental barrier. All of the tetracyclines undergo entero-hepatic cycling. Doxycycline is excreted mainly in feces the other drugs are eliminated primarily in the urine. The half-lives of doxycycline and minocycline are longer than those of other tetracyclines. 

The tetracyclines are a group of antibiotics with the same basic chemical structure they are derivatives of the naphthacene ring system. Compounds of the series differ in the composition of the side chains (Fig. 1). These antibiotics derived from different Streptomyces species show closely related spectra of bacteriostatic properties, with the exception of minocycline, which is very effective against most Staphylococcus strains resistant to other tetracyclines. Absorption, metabolism, and excretion of the different tetracyclines vary, however. After oral application, tetracycline, oxytetracycline, and chlortetracycline are absorbed to a much lesser degree than demethylchlortetracycline, methacycline, or the almost entirely absorbed minocycline. Maximum blood levels are found 2-6 h after oral intake and immediately in the case of intravenous infusion. Half-lives between 8 and 15 h were reported. The tetracyclines diffuse readily across the vascular barrier and are found in various tissues such as the liver, spleen, bone marrow, kidney, skin, and lungs as well as the peritoneal and pericardiac cavities. The tetracyclines are also able to... 

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