Product Description

1 Pharmacodynamic properties

Tetracycline hydrochloride is a broad-spectrum bacteriostatic antibiotic.

Tetracyclines are taken up into sensitive bacterial cells by an active transport process. Once within the cell they bind reversibly to the 30S subunit of the ribosome, preventing the binding of aminoacyl transfer RNA and inhibiting protein synthesis and hence cell growth. Although tetracyclines also inhibit protein synthesis in mammalian cells they are not actively taken up, permitting selective effects on the infecting organism.

2 Pharmacokinetic properties

Most tetracyclines are incompletely absorbed from the gastrointestinal tract, about 60-80% of a dose of tetracycline usually being available. The degree of absorption is diminished by the presence of divalent and trivalent metal ions with which tetracyclines form stable insoluble complexes and to a variable degree by milk or food. Formulation with phosphate may enhance the absorption of tetracycline.

Plasma concentrations will depend upon the degree of absorption. Administration of tetracycline 500mg every 6 hours generally produces steady-state concentrations of 4-5µg/ml. Peak plasma concentrations occur about 1-3 hours after ingestion. Higher concentrations can be achieved after intravenous administration; concentrations may be higher in women than in men.

In the circulation 20-65% of tetracycline is bound to plasma proteins.

They are widely distributed throughout the body tissues and fluids. Concentrations in cerebrospinal fluid are relatively low, but may be raised if the meninges are inflamed. Small amounts appear in saliva, and the fluids of the eye and lung. Tetracyclines appear in the milk of nursing mothers where concentrations may be 60% or more of those in the plasma. They diffuse across the placenta and appear in the foetal circulation in concentrations of about 25 to 75% of those in the maternal blood. Tetracyclines are retained at sites of new bone formation and recent calcification and in developing teeth. The tetracyclines have been classified in terms of their duration of action in the body, although the divisions appear to overlap somewhat.

The tetracyclines are excreted in the urine and in the faeces. Renal clearance is by glomerular filtration. Up to 55% of a dose is eliminated unchanged in the urine; concentrations in the urine of up to 300µg/ml of tetracycline may be reached two hours after a usual dose is taken and be maintained for up to 12 hours. Urinary excretion is increased if urine is alkalinised. The tetracyclines are excreted in the bile where concentrations 5-25 times those in plasma can occur. Since there is some enterohepatic reabsorption complete elimination is slow. Considerable quantities occur in the faeces after administration.

3 Preclinical safety data

Not applicable.