Prevalence of debrisoquine oxidation phenotypes in glaucoma patients.
The oxidation of debrisoquine, a sympatholytic antihypertensive agent, exhibits genetic polymorphism. The debrisoquine/4-OH-debrisoquine metabolic ratio (MR) separates the population to poor (PM, MR greater than 12.6) and extensive (EM, MR less than 12.6) metabolizers. 5-10% of the caucasians belong to the PM phenotype. The oxidation of many other drugs, like timolol, correlates with the debrisoquine phenotype. We determined the debrisoquine phenotype in 102 glaucoma patients. The majority of the patients was treated with ophthalmic timolol. Five patients were classified as PMs. However, two of them were on quinidine, a well known inhibitor of debrisoquine oxidation. The prevalence of debrisoquine PM phenotype in glaucoma patients was 2.9% (excluding patients on quinidine) or 4.9% (with patients on quinidine). The figures are slightly lower than the mean value reported for the normal Finnish population. However, both figures lay within the 95% confidence limits of the prevalence of PM phenotype in the normal Finnish population. The beta-blocking activity of oral timolol is increased in PMs. The significance of timolol oxidation phenotype during ocular timolol therapy warrants further investigation.
Salminen
L
L
Department of Ophthalmology, University of Turku, Finland.
Lindberg
R
R
Toivari
H R
HR
Huupponen
R
R
Kaila
T
T
Iisalo
E
E
D003430:Cross-Sectional Studies; D003647:Debrisoquin / Q000493:pharmacokinetics*; D005901:Glaucoma / Q000188:drug therapy / Q000235:genetics*; D005902:Glaucoma, Open-Angle / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics*; D010084:Oxidation-Reduction / Q000187:drug effects*; D010641:Phenotype; D011110:Polymorphism, Genetic; D013999:Timolol / Q000627:therapeutic use*
D007546:Isoquinolines; D013999:Timolol; D003647:Debrisoquin