Ocular distribution, bactericidal activity and settling characteristics of TobraDex ST ophthalmic suspension compared with TobraDex ophthalmic suspension.
BACKGROUND
TobraDex ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.1%; Alcon Laboratories Inc, Fort Worth, Tex) is frequently used for inflammatory ocular conditions where a risk of bacterial ocular infection exists. A new formulation, TobraDex ST ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.05%, Alcon), utilises a novel suspension technology to reduce viscosity and help prevent settling in the container.


METHODS
A rabbit model that closely mimics the human eye and a clinical study with cataract patients was used to compare the pharmacokinetics and tissue permeability of TobraDex ST and TobraDex. An in-vitro model was used to assess the bactericidal activity using the rabbit tear concentrations of tobramycin 10 minutes after a single topical dose.


RESULTS
Concentrations of both tobramycin and dexamethasone were greater in the tear film and ocular tissues of rabbits treated with TobraDex ST. There was an 8.3-fold increase in tobramycin concentration in the rabbit tear film 10 minutes after dosing with TobraDex ST compared with TobraDex. Concentrations of tobramycin and dexamethasone in ocular tissues from rabbits exposed to TobraDex ST were up to 12.5-fold greater relative to TobraDex. The in-vitro bactericidal activity (>99.9% kill, 3-log reduction) of TobraDex ST toward tobramycin-resistant and methicillin-resistant Staphylococcus aureus occurred in 90 minutes. TobraDex ST killed Streptococcus pneumoniae 3-log in 5 minutes. TobraDex had no activity toward tobramycin-resistant, methicillin-resistant S. aureus and required approximately 120 minutes for 3-log reduction of S. pneumoniae. In humans, the mean ratio of dexamethasone levels in the aqueous humour at 1 hour was 1.17 in favour of TobraDex ST.


CONCLUSIONS
TobraDex ST demonstrated improved suspension formulation characteristics, enhanced pharmacokinetic distribution and improved bactericidal characteristics, and may provide a useful alternative as compared to TobraDex.
Scoper
Stephen V
SV
Virginia Eye Consultants, Norfolk, Virginia, USA.
Kabat
Alan G
AG
Owen
Geoffrey R
GR
Stroman
David W
DW
Kabra
Bhagwati P
BP
Faulkner
Robert
R
Kulshreshtha
Alok K
AK
Rusk
Cindy
C
Bell
Belinda
B
Jamison
Tiffany
T
Bernal-Perez
Lina F
LF
Brooks
Amy C
AC
Nguyen
Vincent A
VA
D000328:Adult; D000818:Animals; D002386:Cataract / Q000378:metabolism; D003907:Dexamethasone / Q000493:pharmacokinetics* / Q000494:pharmacology; D004338:Drug Combinations; D024881:Drug Resistance, Bacterial; D005123:Eye; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D009883:Ophthalmic Solutions / Q000493:pharmacokinetics* / Q000494:pharmacology; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D013535:Suspensions; D013666:Tears / Q000737:chemistry; D014031:Tobramycin / Q000493:pharmacokinetics* / Q000494:pharmacology
D004338:Drug Combinations; D009883:Ophthalmic Solutions; D013535:Suspensions; D003907:Dexamethasone; D014031:Tobramycin