Pharmacotherapeutic group: Antibacterial for systemic use, tetracyclines
Doxycycline is a broad spectrum antibiotic. It inhibits bacterial protein synthesis intracellularly by binding on the 30-S ribosome subunits. This interferes with binding of aminoacetyl-tRNA to the acceptor site on the mRNA ribosome complex and prevents coupling of amino acids to the elongating peptide chains.
Doxycycline inhibits bacteria, Mycoplasma, Chlamydia, Rickettsia, and certain Protozoa.
Four resistance mechanisms acquired by microorganisms against tetracyclines in general have been reported: Decreased accumulation of tetracyclines (decreased permeability of the bacterial cell wall and active efflux), protein protection of the bacterial ribosome, enzymatic inactivation of the antibiotic and rRNA mutations (preventing the tetracycline binding to ribosome). Tetracycline resistance is usually acquired by means of plasmids or other mobile elements (e.g. conjugative transposones). Cross resistance between tetracyclines has also been described. Due to the greater liposolubility and greater facility to pass through cell membranes (in comparison to tetracycline), doxycycline retains a certain degree of efficacy against microorganisms with acquired resistance to tetracyclines.
Doxycycline is quickly and almost completely absorbed from the intestine. The presence of food in the intestine has no effect on the actual absorption of doxycycline. The distribution of doxycycline and penetration of doxycycline throughout most body tissues is good.
Following absorption, tetracyclines are hardly metabolized. In contrast to the other tetracyclines, doxycycline is mainly excreted via the faeces.
After a dosage of 10 mg/kg body weight /day during 5 days, an elimination halftime varying between 15 and 28 hours was found. The doxycycline plasma level reached an average of 2.2 to 2.5 μg/ml.
In pigs, no accumulation of doxycycline in plasma was found after treatment via the drinking water. Mean plasma values of 0.44 ± 0.12 μg/ml after 3 days of medication with an average dose of 10 mg/kg body weight were found.
Steady state plasma concentrations of 2.05 ± 0.47 μg/ml were reached within 6 hours after start of the medication and varied between 1.28 and 2.18 μg/ml with a dosage of 25 mg/kg body weight during 5 days.