Drug absorption behavior after periocular injections.
The purpose of this study was to investigate the absorption behavior of an ophthalmic drug injected in rabbit periocular tissues. After intracapsular, retrobulbar and palpebral conjunctival injections of 150 microl and 50 microl fluorescein isothiocyanate dextran (FITC-dextran, average molecular weight 11000), leakage of the dye into the tear fluid was dependent on the injection route and volume. After periocular injections (50 microl) of tilisolol, as a model beta-blocker, the concentrations in the tear fluid, blood, aqueous humor and vitreous body were determined by HPLC. Slight drug leakage was observed in the tear fluid after injections. The periocular injections showed a faster absorption and a higher area under the concentration-time curve (AUC) in the plasma and a lower AUC in the aqueous humor than those observed in instillation. They also showed a higher ratio of AUC of tilisolol in the vitreous body to AUC in the aqueous humor than that observed in the instillation. Among the periocular injections, retrobulbar injection showed the highest concentrations in the plasma and the lowest in the aqueous humor and vitreous body, while intracapsular injection showed the lowest in the plasma and the highest in the aqueous humor and vitreous body. Although the periocular injections showed a rapid systemic absorption of drug by a rich topical vasculature, it might be an effective approach to deliver the drug to the periocular tissues and vitreous body.
Sasaki
H
H
Department of Hospital Pharmacy, Nagasaki University School of Medicine, Japan.
Kashiwagi
S
S
Mukai
T
T
Nishida
K
K
Nakamura
J
J
Nakashima
M
M
Ichikawa
M
M
D000042:Absorption; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D004333:Drug Administration Routes; D005123:Eye / Q000378:metabolism*; D007546:Isoquinolines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D009883:Ophthalmic Solutions; D011817:Rabbits
D000319:Adrenergic beta-Antagonists; D007546:Isoquinolines; D009883:Ophthalmic Solutions; C036593:tilisolol