Comparison of carteolol plasmatic levels after repeated instillations of long acting and regular formulations of carteolol 2 % in glaucomatous patients

Abstract

Abstract: : Purpose: A new long acting (LA) formulation of carteolol 2% instilled once daily has been shown to provide a therapeutic effect similar to that of the regular formulation of carteolol 2% instilled twice daily. This study was intended to test whether the new formulation reduces the systemic delivery of carteolol. Methods: In this double–masked, randomised, intra–subject comparison study, 23 patients suffering from bilateral primary open angle glaucoma or bilateral ocular hypertension received successively, according to the randomised order of administration, each of the 2 following treatments : carteolol 2% LA once daily for 2 months and carteolol 2% regular twice daily for 2 months. Treatments were systematically instilled in both eyes. At the end of each period of treatment, blood samples were taken just before the last morning instillation (residual time), then 30 minutes, 1 hour, 2 hours and 4 hours after this instillation in order to measure the carteolol plasma concentrations. Results: The mean values of maximal plasmatic concentration (Cmax), residual level and area under the curve obtained following carteolol 2% LA treatment were significantly inferior to the values obtained after carteolol 2% regular treatment (mean ± SD) : Cmax (ng/ml): 1.72 ± 0.85 versus 3.64 ± 3.65; residual level (ng/ml): 0.70 ± 0.58 versus 1.80 ± 0.84; area under the curve (ng/ml x h): 5.50 ± 2.66 versus 10.27 ± 5.46. Both treatments appeared to be well tolerated. Conclusion: Whatever the eye–drops formulation, the plasmatic concentrations found are much lower(about 20 times) than those observed after oral administration of carteolol. According to the data of this study, it can be stated that the systemic delivery of carteolol is lower for the LA formulation than for the regular formulation. The LA formulation of carteolol eye–drops should so reduce the risk of ß–blocking systemic side effects.

Keywords: clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • drug toxicity/drug effects