Penetration of five beta-adrenergic antagonists into the rabbit eye after ocular instillation.

Aqueous humor and serum levels of five beta-adrenergic blockers were measured using gas chromatographic techniques following ocular instillation of 1% solutions to rabbits. Octanol/buffer partition ratios were also determined. No apparent relationship was found between the peak levels of the agents in aqueous humor and their octanol/buffer partition ratios. However, peak aqueous humor levels of timolol (461 ng/100 mg) and practolol (919 ng/100 mg), whose partition ratios were less than unity, occurred somewhat later (1 h) than the peaks of propranolol (859 ng/100 mg at 30 min), oxprenolol (1,771 ng/100 mg at 30 min) or alprenolol (1,004 ng/100 mg at 10 min) whose partition ratios exceeded unity. Peak levels in serum of timolol (8.0 ng/100 microliter), propranolol (4.2 ng/100 microliter), oxprenolol (11.5 ng/100 microliter), and alprenolol (4.5 ng/100 microliter) were achieved within 10 min and reduced to less than 15% within 4 h. Peak serum levels of practolol (9.9 ng/100 microliter) occurred somewhat later (2 h) and remained high (41%) 6 h later.