Tetracyclines differ in their absorption after oral administration and in their elimination. Absorption after oral administration is approximately 60–70% for tetracycline and demeclocycline (not typically used as an antibiotic; see below); 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, alters intestinal flora, and is excreted in the feces. Absorption occurs mainly in the upper small intestine and is impaired by multivalent cations (Ca2+, Mg2+, Fe2+, Al3+); by dairy products and antacids, which contain multivalent cations; and by alkaline pH. Tetracycline and demeclocycline should be administered on an empty stomach, while doxycycline and minocycline absorption is not impaired by food. Specially buffered doxycycline and minocycline solutions are formulated for intravenous administration.
Tetracyclines are 40–80% bound by serum proteins. Oral dosages of 500 mg every 6 hours of tetracycline hydrochloride produce peak blood levels of 4–6 mcg/mL. Peak levels of 2–4 mcg/mL are achieved with a 200-mg dose of doxycycline or minocycline. Steady-state peak serum concentrations of tigecycline are 0.6 mcg/mL at the standard dosage. Tetracyclines are distributed widely to tissues and body fluids except for cerebrospinal fluid, where concentrations are 10–25% of those in serum. Tetracyclines cross the placenta and are also excreted in breast milk. As a result of chelation with calcium, tetracyclines bind to—and damage—growing bones and teeth. Carbamazepine, phenytoin, barbiturates, and chronic alcohol ingestion may shorten the half-life of tetracycline and doxycycline by 50% due to induction of hepatic enzymes that metabolize the drugs.
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 fifty percent of various tetracyclines is excreted into the urine, mainly by glomerular filtration. Ten to forty percent of the drug is excreted in feces. Doxycycline and tigecycline, in contrast to other tetracyclines, are eliminated by nonrenal mechanisms and do not accumulate significantly in renal failure, requiring no dosage adjustment.
Tetracyclines are classified as short-acting (tetracycline, as well as the agricultural agents chlortetracycline and oxytetracycline), intermediate-acting (demeclocycline), 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 for certain indications, but, by convention, these two drugs are usually dosed twice daily.