Use
Absorption
Tetracyclines are usually administered by mouth. However,
tigecycline is available only for intravenous infusion.
Absorption of oral tetracyclines occurs largely in the
proximal small bowel, but may be diminished by the simultaneous
presence of food, milk or cations, which form nonabsorbable
tetracycline chelates. Cimetidine and presumably
other H2-receptor antagonists also impair absorption of
tetracyclines
by interfering with their dissolution, which is
pH dependent.
The absorption problems of earlier compounds have been
essentially overcome in the later tetracyclines. Improved
absorption is claimed for lymecycline, demeclocycline and
methacycline, but is best established for doxycycline and
minocycline, which may be administered with food and for
which the proportion of administered dose absorbed is more
than 90%.
Distribution
For orally administered tetracyclines, peak serum concentrations
follow 1–4 h after ingestion. Serum levels achieved
after normal dosage of orally bioavailable tetracyclines are of
the order of 1.5–4.0 mg/L. Most tetracyclines must be given
four times daily to maintain therapeutic concentrations in the
blood, but demeclocycline and minocycline can be administered
twice daily and doxycycline once daily.
Tetracyclines penetrate moderately well into body fluids
and tissues, reflected in relatively large volumes of distribution.
Concentrations of most tetracyclines in the cerebrospinal
fluid (CSF) are usually about 10–25% of those in the
blood, although penetration of tigecycline into the CSF is
poor. A unique feature of tetracyclines is deposition and persistence
in areas where bone is being laid down. Radioactive
tracer studies in animals suggest that tigecycline also concentrates
in the bone but concentration at this site in humans
remains unproven owing to technical difficulties with assay
methods.
Older tetracyclines are known to penetrate into the
sebum and are excreted in perspiration, properties which
contribute to their usefulness in the management of acne.
The older tetracyclines
are also known to be concentrated
in the eye.
Excretion
Excretory routes are the kidney and feces. Fecal excretion
occurs even after parenteral administration as a result
of passage of the drug into the bile. The concentrations
obtained in bile are 5–25 times those in the blood, doxycycline
attaining especially high levels. These concentrations
are lowered in the presence of biliary obstruction. The proportion
of administered dose found in the urine is, for most
tetracyclines, in the range 20–60%, but is less for chlortetracycline
and doxycycline and least for minocycline and
tigecycline.