Pharmacology and toxicology of doxycycline

Abstract

Doxycycline, a structural isomer of tetracycline, has been used in human medicine since 1966. The molecule, obtained semi-synthetically from oxytetracycline or methacycline, is highly lipophilic permitting excellent penetration into tissues. In vitro antimicrobial activity of doxycycline is superior to that of the older tetracyclines (chlortetracycline, oxytetracycline, tetracycline). In laboratory animals, the protective dose for 50% of the subjects (PD50) demonstrates a better in vivo activity than that of all other members of the tetracycline family. Clinical use in human medicine has confirmed the efficacy of doxycycline for a variety of infectious conditions. High lipophilicity results in a large volume of distribution, substantial binding to plasma proteins, and reabsorption in the renal tubules and gastrointestinal tract, thereby conferring a long elimination half-life to the drug. Excellent absorption after oral administration allows small oral doses and minimizes the known side effects of tetracyclines on the gastrointestinal tract--irritation and suprainfection. The contrast to the other tetracyclines, doxycycline does not accumulate in renal failure due to a compensatory gastrointestinal secretion. The pharmacology, toxicology and therapeutics of doxycycline in laboratory animals and man indicate that this drug may be a valuable antimicrobial for use in veterinary medicine.