Doxycycline absorption

Absorption from the gastrointestinal tract can be affected by other drugs and by food. Aluminum, calcium, and magnesium ions in antacids or dairy products form insoluble chelates with all tetracyclines and inhibit their absorption. Food inhibits tetracycline absorption but enhances doxycycline absorption food delays but does not diminish metronidazole absorption fatty food enhances griseofulvin absorption. 

Administration of 100 mg doxycycline, in the absence of foods, led to almost complete absorption from the gut and a peak blood level of 1-8 Mg/ml two hours after ingestion. Three times this dose was required.to produce a similar blood level in four hours in the case of 300 mg demethylchlortetracycline. The plasma half-life (after single dose) was 15 hours in the case of doxycycline and 12 hours for demethylchlortetracycline. This means that the half-life of doxycycline is seven hours longer than that of tetracycline. 

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... 

These antibiotics are partially absorbed from the stomach and upper gastrointestinal tract. Food impairs absorption of all tetracyclines except doxycycline and minocycline. Absorption of doxycycline and minocy-cbne is improved with food. Since the tetracyclines form insoluble chelates with calcium (such as are found in many antacids), magnesium, and other metal ions, their simultaneous administration with milk (calcium), magnesium hydroxide, aluminum hydroxide, or iron will interfere with absorption. Because some of the tetracyclines are not completely absorbed, any drug remaining in the intestine may inhibit sensitive intestinal microorganisms and alter the normal intestinal flora. 

The absorption of tetracycline administered orally is variable and depend upon the type of tetracycline used. The tetracycline form insoluble complexes i.e. chelation with calcium, magnesium, milk and antacids reduce their absorption. Administration of iron also interferes with the absorption of tetracycline. Doxycycline is rapidly and virtually completely absorbed after oral administration and its absorption is not affected by presence of food or milk. 

Because of virtually complete absorption of doxycycline and minocycline side effects pertaining to the lower bowel, particularly... 

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. 

Doxycycline Oral and IV longer half-life (18 h) so dosed twice daily nonrenal elimination absorption is minimally effected by divalent cations used to treat community-acquired pneumonia and exacerbations of bronchitis... 

Tetracyclines are rapidly but moderately absorbed from the gastrointestinal tract. The degree of oral absorption of the various tetracyclines is also a function of the lipophilicity of the particular compound. The least lipophilic oxytetracycline is the least well absorbed and the most lipophilic doxycycline is the best absorbed, whereas the absorption of the other tetracyclines falls between these two extremes. 

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). 

DOXYCYCLINE H2 RECEPTOR BLOCKERS i plasma concentrations and risk of treatment failure i absorption of cephalosporin as T gastric pH Avoid concomitant use. If unable to avoid combination, take H2 antagonists at least 2-3 hours after cephalosporin. Consider an alternative antibiotic or separate the doses by at least 2 hours and give with an acidic drink, e.g. carbonated drink T dose may be required... 

Milk and dairy foods decrease the absorption of some tetracyclines (doxycycline and minocycline are not affected), some quinolone antibiotics (absorption of ciprofloxacin and norfloxacin is decreased but ofloxacin is not affected), penicillamine and alendronate. Large volumes of milk can reduce the ulcer-healing properties of bismuth tripotassium dicitratobismuthate (bismuth chelate),... 

Antibiotics. Long-term administration of antibiotics could lead to vitamin B6 deficiency, If symptoms of peripheral neuropathy develop (numbness and tingling of the extremities), administer vitamin B6. Sulfasalazine can decrease the absorption of folic acid, and trimethoprim can cause folate deficiency, hence the need to administer folic acid if there is evidence of deficiency. Rifampicin can cause disturbances in vitamin D metabolism and lead to osteomalacia. The absorption of tetracyclines can be reduced by calcium, magnesium, iron and zinc, while this antibiotic could also decrease the absorption of these minerals. This effect is probably least with minocycline and is not confirmed with doxycycline. Doses of minerals and antibiotic should be separated by at least 2 hours. The absorption of quinolones is reduced by cationic and anionic supplements. 

Bind to other drugs that are administered within 1 or 2 hours of the antacid, This process results in reduced availability of the co-administered drug for absorption, For example, the chelation of tetracyclines (e.g, tetracycline, doxycycline) will decrease their absorption by up to 90%, Avery similar process - precipitation - occurs with drugs such as quinine with aluminium and magnesium hydroxide preparations, which results in a decreased absorption of quinine, It has to be noted that the absorption of fluoroquinolones (e g. ciprofloxacin, norfloxacin, ofloxacin, enoxacin, perfloxacin i will be decreased by 60-75% if they are co-administered with divalent and trivalent cations. Patients are recommended not to take these divalent and trivalent cationic preparations until fluoroquinolone therapy is discontinued. 

The administration of tetracycline with food can ameliorate its irritative effects, bnt food can adversely affect the drug s absorption. In contrast, the absorption of doxycycline is only slightly affected by the presence of food, including dairy prodncts. Becanse all tetracyclines can form complexes with divalent cations, the absorption of any tetracycline is markedly decreased when administered with iron-containing tonics or antacids containing calcium, magnesium, or aluminum. Sodium bicarbonate also adversely affects tetracycline absorption. 

The presence of food in the GI tract reduces the absorption of many antiinfective agents. Although there are some exceptions (e.g., penicillin V, amoxicillin, and doxycycline), it is generally recommended that penicillin and tetracycline derivatives, as well as certain other antiinfective agents, be given at least 1 h before meals or 2 h after meals to achieve optimum absorption. 

Doxycycline and minocycline are more lipophilic tetracyclines. They are well absorbed after oral administration. Their half-lives are 16-18 hours. Their higher affinity for fatty tissues improves their effectiveness and changes their adverse effects profile. Local gastrointestinal irritation and disturbance of the intestinal bacterial flora occur less often than with the more hydrophilic drugs, which have to be given in higher oral doses for sufficient absorption. 

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. 

Ericsson C D, Feldman S, Pickering L K et al 1982 Influence of subsalicylate bismuth on absorption of doxycycline. Journal of the American Medical Association 247 2266-2267 Ericsson C D, Tannenbaum C, Charles T T 1990 Antisecretory and antiinflammatory properties of bismuth subsalicylate. Reviews of Infectious Diseases 12 (suppi 1) S16-S20... 

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