Doxycycline distribution

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 distributed throughout body tissues and fluids in concentrations that reflect the lipid solubility of each individual agent. Minocycline and doxycycline are the most lipid soluble, while oxytetracy-chne is the least hpid soluble. The tetracyclines penetrate (but somewhat unpredictably) the uninflamed meninges and cross the placental barrier. Peak serum levels are reached approximately 2 hours after oral administration cerebrospinal fluid (CSF) levels are only one-fourth those of plasma. 

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. 

From residue data with pigs, poultry, and cattle after oral administration, and with cattle after intravenous administration, it appears that the distribution profde of doxycycline in these animals is roughly comparable to that of oxytetracycline. Highest residue concentrations are found in kidney, followed by liver, skin, fat, and muscle. Tissue depletion studies in pigs treated intramuscularly with doxycycline at a 10 mg/kg bw dose for 4 days showed that the parent compound was absorbed and efficiently distributed in tissues (252). The concentrations of doxycycline detected in lung, muscle, liver, and kidney tissues at day 6 after treatment were 0.067, 0.047, 0.18, and 0.47 ppb, respectively detectable doxycycline residues were not present in fat at that withdrawal time. 

Doxycycline is the preferred tetracycline because it is better absorbed and distributed than the others. 

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. 

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 are distributed into most tissues, except the CNS (therapeutic levels may be achieved when the meninges are inflamed). Doxycycline is the most lipid-soluble tetracycline... 

Preliminary studies using the IPPSF have shown that compounds such as the cancer chemotherapeutic agents cisplatin and carboplatin and the antibiotics tetracycline and doxycycline readily distribute into the skin following intravascular administration. Also, compounds such as parathion, 1-aminobenzo-triazole (ABT), and 25-hydroxyvitamin D are bioactivated in the skin following intravascular administration in the IPPSF. This demonstrates a role for the IPPSF as an ideal experimental model for studying the disposition of xenobiotics that are... 

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. 

An in vitro study found that doxycycline potentiated the antimalarial activity of atovaquone, but there appears to be no information on the effect of doxycycline on the absorption of atovaquone. A study looking at the population pharmacokinetics of atovaquone in 24 Thai patients found that neither the oral clearance nor the volume of distribution of atovaquone were significantly affected by the concurrent use of tetracycline. ... 

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