Doxycycline elimination

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. 

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... 

The serum-protein binding ability, which varies between animals and is also influenced by the disease state of the animal, will also determine the free diffusible concentration. This, in turn, will have an effect on the elimination of drug residues as well as on their penetration in eggs or milk. This effect will be more pronounced for drugs with a higher tendency for protein binding such as sulfonamides, doxycycline, and cloxacillin (47). 

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. 

Vibrio cholerae. The cause of death in cholera is electrolyte and fluid loss in the stools and this may exceed 11/h. The most important aim of treatment is prompt replacement and maintenance of water and electrolytes with oral or intravenous electrolyte solutions. Doxycycline, given early, significantly reduces the amount and duration of diarrhoea and eliminates the organism from the faeces (thus lessening the contamination of the environment). Carriers may be treated by doxycycline by mouth in high dose for 3 days. Ciprofloxacin may be given for resistant organisms. 

Minocycline and doxycycline are predominantly eliminated by the liver and biliary tract (70-90%). Therefore, no change in dose is needed in patients with impaired renal function. However, it should be considered that hepatic elimination of doxycychne or minocycline might be accelerated by co-administration of agents that induce hepatic enzymes. 

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 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. 

Doxycycline is more lipid-soluble than other tetracyclines and less dependent on renal elimination more than 50% of the drug is eliminated in the feces. 

The majority of drugs are eliminated through the urine. Exceptions are the lipophilic drugs such as doxycycline and minocycline. 

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. 

Antimicrobial drugs that are eliminated via hepatic metabolism or biliary excretion include erythromycin, cefoperazone, clindamycin, doxycycline, isoniazid, ketoconazole, and nafcillin. The answer is (C). 

A study in 8 healthy subjects found that tetracycline 500 mg twice daily for 7 days increased the maximum plasma levels, AUC and elimination half-life of a single 500-mg dose of halofantrine by 146%, 99%, and 73%, respectively. Increases in the major metabolite of halofantrine also occurred in the presence of tetracycline. As both halofantrine and tetracycline are excreted into the bile, competition for this elimination route may result in increased plasma levels. There may be an increased risk of halofantrine toxicity if it is used with higher doses of tetracycline. In contrast, in vitro studies found that doxycycline does not inhibit the metabolism of halofantrine. ... 

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