Comparison of carteolol plasmatic levels after repeated instillations of long-acting and regular formulations of carteolol 2% in glaucoma patients
- 89 Downloads
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.
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.
The mean values of maximal plasma concentration (Cmax), 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): 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×h): 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.
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 β-blocking systemic side effects.
KeywordsCarteolol Beta-blocker Alginic acid Systemic delivery Kinetics
The authors would like to thank R. Garraffo, pharmacist, France, for his advice on pharmacokinetics; C. Whately-Smith, statistician, UK, for reviewing the article; and all the study participants.
- 3.Ishii Y, Nakamura K, Matsuki S, Uemura N, Muraguchi R, Nakagawa M, Nakano S, Nakatsuka K (2002) Pharmacokinetic and pharmacodynamic differences between ocular and nasal instillation of carteolol on intraocular pressure and heart rate in Japanese men with high CYP2D6 activity. J Clin Pharmacol 42:1020–1026PubMedGoogle Scholar
- 6.Morita S, Iinuma M, Kido M, Sakuragi S, Kohri H, Nishino H (1977) Metabolic fate of carteolol hydrochloride, (OPC-1085) VIII, a new β-adrenergic blocking agent. Drug Res 27:2380–2383Google Scholar
- 7.Negishi C, Kanai A, Nakajima A, Funahashi M, Kitazawa Y (1981) Ocular effects of beta-blocking agent carteolol on healthy volunteers and glaucoma patients. Jpn J Ophthalmol 25:464–476Google Scholar
- 9.Note for guidance on the investigation of bio-availability and bio-equivalence. E.M.E.A. 2001Google Scholar
- 10.Ringham GL, Luther RR, Senello LT, Schambelan M, Humphreys MH (1985) A pharmacokinetic evaluation of carteolol in patients with impaired renal function. J Clin Pharmacol 25:468Google Scholar
- 11.Ringham GL, Senello LT, Jordan DC, Luther RR, Klepper MJ, Finley RA, Tolman KG (1987) Pharmacokinetics of carteolol in subjects of different ages. J Clin Pharmacol 27:715Google Scholar
- 13.Senello LT, Finley RA, Chu SY, Bunnell ST, Sonders RC, Ringham GL, Luther RR, Humphreys MH, Poon AH, Schambelan M (1987) The effect of impaired renal function on the multiple dose clinical pharmacokinetics of carteolol. Adv Ther 4:298–308Google Scholar