The effect of vehicle on corneal penetration of triturated ketoconazole and itraconazole.
OBJECTIVE
Triturated (crushed and suspended) ketoconazole has been recommended for the treatment of fungal keratitis when commercial antifungal eyedrops are unobtainable. The authors evaluated the in vivo corneal stromal concentration with different vehicles in the eyes of adult rabbits.


METHODS
Ketoconazole and itraconazole tablets were triturated to 20 mg/ml in four vehicles: polyvinyl alcohol (PVA), boric acid, olive oil, and balanced salt solution (BSS). Six eyes (deepithelialized for better penetration) received one drop every 15 minutes for 2 hours. A yeast overlay bioassay of extracts determined the stromal concentration.


RESULTS
Itraconazole in BSS, olive oil, PVA, and boric acid produced inhibition zones of 17.3, 15.6, 15.4, and 13.2 mm, respectively. Ketoconazole produced inhibition zones of 35.9, 39.4, 41.8, and 44.7 mm, respectively. From a standard curve, the concentrations of ketoconazole in tissue were 512, 773, 1221, and 1492 micrograms/g, respectively.


CONCLUSIONS
The vehicle that is used to triturate antifungals affects the tissue concentration. This may have an impact on fungal keratitis therapy.
Guzek
J P
JP
Department of Ophthalmology, Jerry L. Pettis Memorial Veterans Administration Hospital, Loma Linda, CA, USA.
Roosenberg
J M
JM
Gano
D L
DL
Wessels
I F
IF
D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D003319:Corneal Stroma / Q000378:metabolism*; D005500:Follow-Up Studies; D017964:Itraconazole / Q000493:pharmacokinetics*; D007654:Ketoconazole / Q000493:pharmacokinetics*; D009883:Ophthalmic Solutions; D014677:Pharmaceutical Vehicles / Q000494:pharmacology*; D011817:Rabbits
D000935:Antifungal Agents; D009883:Ophthalmic Solutions; D014677:Pharmaceutical Vehicles; D017964:Itraconazole; D007654:Ketoconazole