Evaluation of aqueous humor concentrations of Istalol and Betimol following a single ocular instillation in rabbit eyes.

PURPOSE: The aim of this study was to evaluate the pharmacokinetic absorption profiles of two commercially available ophthalmic solutions following a single instillation into each eye of New Zealand white rabbit eyes. METHODS: A single dose of either timolol maleate with potassium sorbate (TLA) or timolol hemihydrate (THH) was instilled into each eye of New Zealand white rabbits (15 rabbits/drug preparation, 50-microL dose). Animals were euthanized 15, 30, 60, 120, and 180 min after instillation, with 3 animals/drug/time intervals. Aqueous humor from both eyes of each animal was pooled and analyzed for timolol concentration, using the high-performance liquid chromatography method. RESULTS: TLA reached a mean peak concentration of 3.705 +/- 0.3012 microg/mL at 15 min, tapering to 0.539 +/- 0.1431 microg/mL by 180 min. THH reached a mean peak concentration of 2.239 +/- 0.1430 microg/mL at 15 min postinstillation, tapering to 0.148 +/- 0.0282 microg/mL by 180 min. CONCLUSIONS: TLA containing potassium sorbate demonstrated an absorption profile of more rapid absorption (1.7 fold greater at 15 minutes) and longer residences time (3.6 fold greater at 180 minutes) than the THH. At every time point throughout the study, TLA demonstrated greater drug concentration than THH.

24-hour evaluation of the ocular distribution of (14)C-labeled bromfenac following topical instillation into the eyes of New Zealand White rabbits.

PURPOSE: The aim of this study was to determine the distribution and concentrations of bromfenac ophthalmic solution in ocular tissues following topical instillation in New Zealand White (NZW) rabbits. DESIGN: Two animal studies were conducted. METHODS: A single 50-muL (14)C-bromfenac ophthalmic solution (20-25 muCi or 0.09%) was administered into the right eyes of 14-18 randomly assigned NZW rabbits. At various time points, ocular tissues were collected and analyzed for (14)C-bromfenac contents. Ocular tissues were combusted and the amount of radioactivity was determined by liquid scintillation counting (LSC). Aqueous-humor samples were directly transferred to LSC vials. RESULTS: Peak concentrations of (14)C-bromfenac were observed in the aqueous humor and most ocular tissues at or before 2-hours. The highest concentrations were in the cornea, conjunctiva, and sclera. Similar amounts were detected in the aqueous humor, iris-ciliary body, choroid, and, to a slightly lesser degree, in the retina. Measurable amounts of bromfenac were detected in all samples at the 24-hours time point (> or =0.001 mug equivalent/g). CONCLUSIONS: Significant penetration and measurable amounts of (14)C-bromfenac were detected in all ocular tissues over 24 h, including the sclera, choroid, and retina. These results strongly suggest the utility of bromfenac ophthalmic solution 0.09% in treating inflammation of both the anterior and posterior ocular segments.

Lack of medication dose uniformity in commonly split tablets.

OBJECTIVE: To divide 11 commonly split tablets and evaluate the resulting half-tablets for content uniformity. DESIGN: Pre-post comparison. SETTING: Laboratory. INTERVENTIONS: A trained individual split tablets of 11 products using a single-edged razor blade and 3 products by hand alone. MAIN OUTCOME MEASURES: The Uniformity of Dosage Units test published in the United States Pharmacopeia 24 (USP), which applies to whole tablets, was adapted liberally to assess the dose uniformity of the resulting split tablets. RESULTS: Of the 11 razor-split products, 8 failed the liberal adaptation of the USP uniformity test. No visible tablet features (e.g., scoring) predisposed a product's split tablets to pass or fail the uniformity test. All three hand-split tablets failed the uniformity test and yielded worse results than did razor-split tablets. CONCLUSION: The majority of the 11 drug products we tested, when assessed for their ability to be split into half-tablets of equal dose, failed a liberally interpreted USP uniformity test. The practice of dividing tablets to save costs or to improve a dosage regimen may not cause problems for patients using drugs with low toxicity and relatively flat dose-response relationships, but it is not recommended for patients using drugs with more substantial toxicity and steep dose-response efficacy curves.