24-Hour Intraocular Pressure Control with Fixed-dose Combination Brinzolamide 1%/Brimonidine 0.2%: A Multicenter, Randomized Trial.

PURPOSE: To determine the intraocular pressure (IOP)-lowering effect of fixed-combination brinzolamide 1%/brimonidine 0.2% (BBFC) over a 24-hour period. DESIGN: Prospective, multicenter, double-masked, parallel-group clinical trial conducted at 16 academic and nonacademic sites in the United States. PARTICIPANTS: Subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT) aged ≥18 years with mean baseline IOP measurements in at least 1 eye of ≥21 and <28 mmHg. METHODS: Duplicate mean pneumatonometer IOP measurements were collected every 2 hours over a 24-hour period in controlled light conditions in overnight facilities. Daytime (8 am-8 pm) and nocturnal (10 pm-6 am) IOP measurements were collected in a sitting or supine position, respectively. Baseline 24-hour IOP was measured in untreated subjects after a washout (up to 4 weeks) and eligibility phase. After the baseline visit, participants were randomized 1:1 to receive masked BBFC or vehicle, 1 drop 3 times daily (8 am, 3 pm, and 10 pm) for 4 weeks. At week 4, IOP measurements were repeated in both groups under the same conditions. MAIN OUTCOME MEASURE: Mean change from baseline in 24-hour IOP at week 4. RESULTS: Of 125 participants randomized, 123 (98%; BBFC, n = 62; vehicle, n = 61) completed the study. No subjects randomized to BBFC discontinued the study. At week 4, BBFC-treated eyes had significantly reduced mean 24-hour IOP vs. vehicle (least squares mean difference [95% confidence interval]: -2.5 [-3.3, -1.7]; P < 0.001); daytime (-3.4 [-4.3, -2.6]; P < 0.001) and nocturnal (-1.2 [-2.3, 0.0]; P = 0.053) reductions were observed. Mean change from baseline was significantly different between BBFC- and vehicle-treated eyes at all daytime points and 3 of 5 nocturnal time points (10 pm, 12 am, and 6 am; secondary end point). The frequency of adverse events was similar between treatment groups; in the BBFC arm, ocular hyperemia, corneal abrasion, and dysgeusia were the most frequently reported, consistent with events described in the drug label. CONCLUSIONS: This large, multicenter study of 24-hour IOP control with BBFC met its primary end point; BBFC demonstrated significantly superior 24-hour IOP-lowering efficacy versus vehicle after 4 weeks of 3-times-daily treatment in subjects with OAG or OHT.

Transfer of L-alpha-acetylmethadol (LAAM) and L-alpha-acetyl-N-normethadol (norLAAM) by the perfused human placental lobule.

The agonists buprenorphine and l-alpha-acetylmethadol (LAAM) were introduced as alternatives to methadone for treatment of the adult opiate addict. The direct and indirect effects of these drugs on normal fetal growth and development are currently under investigation in our laboratory. The goal of this report is to provide part of the data necessary to assess the safety of LAAM in treatment of the pregnant opiate addict. To achieve this goal, the technique of dual perfusion of placental lobule was utilized to determine the kinetics for transplacental transfer of LAAM and its effects on the viability and functional parameters of the tissue. LAAM is rapidly metabolized to the pharmacologically active norLAAM that was also included in this investigation. The two opiates were transfused at their plasma levels in patients under treatment, a concentration of 35 ng/ml. The drugs exhibited similar pharmacokinetic profiles, characterized by an initial phase of distribution into placental tissue followed by their low transfer to the fetal circuit. During the 4-h experimental period, the transfused tissue retained significant amounts of LAAM and norLAAM, and neither drug was metabolized. LAAM did not affect placental tissue viability and functional parameters. However, norLAAM caused a significant decrease in the release of human chorionic gonadotropin. At this time, it is unclear whether a similar effect for norLAAM may occur in vivo and, if so, what the consequences would be on its role in implantation and normal fetal growth and development.