Penetration of ocular compartments by tetracyclines

Abstract

Total antibiotic concentration of tetracycline hydrochloride was determined in the ocular structures of rabbits by radioactive tracer method. Concentration of tetracycline of 0.1 to 5 microgram/g, adequate to inhibit the growth of bacteria of high or medium susceptibility, was measured from all ocular structures with the exception of the lens. Tetracycline concentration in the aqueous humor was inferior to that in the vascularized ocular tissues and to that in the cornea. Vitreous body tetracycline level, about 0.3 microgram/g, was about half of the concentration in the aqueous humor. The disruption of the blood-aqueous barrier following paracentesis led to an immediate increase of tetracycline concentration in the anterior structures of the eye.

Ocular penetration of oral doxycycline in the horse

“…As mentioned above, it is probable that the concentration gradient between blood and the eye after oral administration was too low to promote diffusion of doxycycline. Although documented in humans, 29 there is limited information on the penetration of doxycycline into the normal eye following oral administration in animals. Previous studies in normal dogs and rabbits reported distribution of doxycycline into both aqueous and vitreous after intravenous administration 28–31 .…”

“…Although documented in humans, 29 there is limited information on the penetration of doxycycline into the normal eye following oral administration in animals. Previous studies in normal dogs and rabbits reported distribution of doxycycline into both aqueous and vitreous after intravenous administration 28–31 . Intravenous administration usually produces higher serum concentrations and larger concentration gradients for diffusion into peripheral tissues.…”

“…It is possible also that binding of doxycycline to plasma proteins may have limited distribution into the aqueous and vitreous, which have lower protein concentrations 29 . Fluconazole, a drug that achieves very high aqueous concentrations following oral dosing in the horse, is minimally protein bound 32 .…”

“…Fluconazole, a drug that achieves very high aqueous concentrations following oral dosing in the horse, is minimally protein bound 32 . It is important to note that in a study measuring doxycycline concentration in normal rabbit ocular tissue, although the aqueous and vitreous concentrations were relatively low (< 0.5 and < 0.3 µg/g, respectively), the concentration in the iris and ciliary body approached serum concentrations (0.7–2 µg/g), and the concentration in the retina and choroid exceeded serum concentrations (1.5–5 µg/g) 29 . It is possible that these tissue concentrations are more clinically relevant, especially in chronic leptospiral infections in which intracellular sequestration of the bacteria occurs.…”

Prostaglandin-based rAAV-mediated glaucoma gene therapy in Brown Norway rats

“…The expression cassette is flanked by inverted terminal repeats (ITRs) derived from AAV2 to allow packaging into a recombinant rAAV vector, and also contains two 'off-type' tetracyclineresponsive riboswitch elements (TC40 and TC45), which we have demonstrated previously allow for post-transcriptional downregulation of transgene expression from a rAAV vector injected into the eye upon oral dosing of the activating ligand (i.e., tetracycline) 45,46 . While the TC40 and TC45 riboswitches have not been expressed in cells of the anterior chamber, it is known that tetracycline accumulates within the cornea and aqueous humor following oral dosing and as such, is expected to be bioavailable to the riboswitch elements to drive gene modulation 47 . The inclusion of an off-switch in the expression cassette is a critical consideration for the development of any prostaglandin-based IOP lowering gene therapy treatment, where clinical management of OAG can necessitate temporary cessation of PGF 2α treatment in the event of a patient developing a concurrent infection, such as herpetic keratitis 18,48,49 .…”