Abstract
Purpose: :
Oral propranolol is an effective treatment for periocular infantile capillary hemangiomas (ICH). We previously reported higher concentrations of propranolol in periocular tissues and lower peripheral blood levels of drug after topical, ocular instillation of propranolol as compared with oral delivery (Hao et al 2011). The delivery of propranolol in a gel-forming solution (GFS) may further increase the local tissue concentration of propranolol while decreasing systemic exposure to the drug as compared with a non-GFS. We compared the periocular tissue concentration and plasma concentration of propranolol after ocular instillation of propranolol 0.5% in GFS and in non-GFS
Methods: :
Propranolol was delivered by topical, ocular instillation of 0.15 ml (50 μl x 3 doses) of propranolol (0.5%) in phosphate buffered saline solution or propranolol (0.5%) in 1% sodium alginate gel-forming solution (GFS) for total of 0.75 mg in the treated eye of New Zealand male white rabbits (2 to 2.5 kg body weight). Rabbits were sacrificed at 1, 4, 8 and 24 hours after drug instillation. HPLC was used to analyze peripheral blood and periocular tissues, which were dissected and separately analyzed as upper lid inner, upper lid outer, lower lid inner, and lower lid outer layers; bulbar conjunctiva; superior rectus and oblique; inferior rectus and oblique; medial and lateral rectus; and periocular fat. Peripheral blood samples were also analyzed by HPLC.
Results: :
At 1 h post dosing, propranolol in GFS resulted in similar or higher concentrations of propranolol in most periocular tissues (except inferior rectus and oblique) as compared with propranolol in non-GFS. By 8 h, most tissue types had higher concentrations of drug in the GFS group. The plasma concentration of drug was lower in the GFS group at 1h, and both GFS and non-GFS groups had undetectable drug levels in plasma by 4 to 8 h.
Conclusions: :
Ocular delivery of propranolol in a GFS resulted in similar or higher concentration of propranolol in most periocular tissues as compared to non-GFS. The finding of higher tissue concentrations with GFS may be due to prolonged retention of drug on, and decreased clearance of the drug from, the ocular surface. Lower systemic exposure to propranolol when using GFS may decrease the risk of systemic side effects from the drug.
Keywords: drug toxicity/drug effects • tumors