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

Graefes Arch Clin Exp Ophthalmol. 2005 Dec;243(12):1221-7. doi: 10.1007/s00417-005-0024-5. Epub 2005 Jul 8.

Abstract

Background: 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 designed to test whether the new formulation reduces the systemic delivery of carteolol.

Methods: In this double-masked, randomised, intra-subject comparative study, 23 patients with bilateral primary open-angle glaucoma or bilateral ocular hypertension received sequentially, 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 instilled in both eyes throughout the study period. At the end of each period of treatment, blood samples were taken immediately before the last morning instillation (residual time), then 30 min, 1 h, 2 h and 4 h after this instillation in order to measure the carteolol plasma concentrations.

Results: The mean values of maximal plasma concentration (C(max)), residual level and area under the curve obtained following carteolol 2% LA treatment were significantly lower than the values obtained after carteolol 2% regular treatment (mean+/-SD): C(max) (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/mlxh): 5.50+/-2.66 versus 10.27+/-5.46. Regarding safety, two drug-related, non-serious adverse events were reported in the LA group: one case of moderate, superficial, punctate keratitis and one case of "bitter taste in the throat." Both treatments appeared to be well tolerated.

Conclusions: The data from this study showed that the systemic delivery of carteolol is lower for the once-daily LA formulation than for the regular twice-daily formulation. Consequently, long-acting carteolol eye-drops should reduce the risk of beta-blocking systemic side effects.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / pharmacokinetics*
  • Aged
  • Aged, 80 and over
  • Carteolol / administration & dosage
  • Carteolol / pharmacokinetics*
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Double-Blind Method
  • Female
  • Glaucoma, Open-Angle / blood*
  • Glaucoma, Open-Angle / drug therapy
  • Glaucoma, Open-Angle / physiopathology
  • Humans
  • Instillation, Drug
  • Intraocular Pressure / drug effects
  • Male
  • Middle Aged
  • Ocular Hypertension / blood
  • Ocular Hypertension / drug therapy
  • Ocular Hypertension / physiopathology
  • Treatment Outcome

Substances

  • Adrenergic beta-Antagonists
  • Delayed-Action Preparations
  • Carteolol