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Pharmacokinetic and Pharmacodynamic Differences between Ocular and Nasal Instillation of Carteolol on Intraocular Pressure and Heart Rate in Japanese Men with High CYP2D6 Activity
Author(s) -
Ishii Yoko,
Nakamura Koichi,
Matsuki Shunji,
Uemura Naoto,
Muraguchi Ryoko,
Nakagawa Mikiko,
Nakano Shigeyuki,
Nakatsuka Kazuo
Publication year - 2002
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127000204200909
Subject(s) - medicine , intraocular pressure , pharmacodynamics , ocular hypertension , anesthesia , crossover study , pharmacokinetics , nostril , ophthalmology , nose , pharmacology , surgery , placebo , alternative medicine , pathology
Sublingual administration of carteolol or instillation into one eye reduces intraocular pressure (IOP) in both eyes. This suggests that carteolol absorbed systemically can reduce IOP and that the extra‐ophthalmic route (e.g., the nasal route) can be an alternative method of drug administration. The authors compared the differences between ocular and nasal instillation relating to the pharmacokinetic and pharmacodynamic effects of a carteolol‐ophthalmic solution on IOP and heart rate (HE) in a randomized, double‐blind, crossover, placebocontrolled design in 11 healthy young extensive metabolizers for CYP2D6. The t max' C max' and AUC o‐t of carteolol (0.8 mg) instilled into the nostril were significantly higher than those into the eye (p < 0.05): t max (h)= 0.25 (0.17‐5.0), 1.0 (0.17‐5.0) (median value with range in the parenthesis, ocular vs. nasal); C max (ng/ml) = 1.33 ± 1.57, 2.29 ± 2.09; and AUC o‐t (ng•h/ml) = 9.36 ± 2.04, 21.13 ± 1.58 (geometric mean ± SD, ocular vs. nasal). The reduction of IOP after ocular instillation persisted significantly longer than that of nasal instillation (p < 0.05). The HR was significantly reduced after both ocular and nasal instillation (p < 0.05), although there were no significant differences between them. In conclusion, ocular instillation of a carteolol‐ophthalmic solution has advantages over nasal instillation in controlling IOP and the potential to decrease adverse reactions due to lower plasma concentrations .