Systemic absorption of ocular timolol in poor and extensive metabolizers of debrisoquine.
The oxidation of timolol exhibits genetic polymorphism of debrisoquine type. After oral administration, poor metabolizers have high timolol concentrations in plasma and show an intensified systemic beta-blockade. Since the contribution of debrisoquine metabolizer status on timolol eyedrop therapy is not known we determined the systemic absorption of ocularly applied timolol in healthy subjects classified either extensive or poor metabolizers. Unlike after oral timolol ocular drug administration caused higher peak drug concentrations in plasma in extensive metabolizers. The variation in the systemic absorption of ocular timolol contributed more than the debrisoquine oxidation phenotype to timolol plasma levels after a single ocular timolol application.
Department of Clinical Pharmacology, University of Turku, Finland.
R
R
Huupponen
T
T
Kaila
K
K
Lahdes
L
L
Salminen
E
E
Iisalo
D000042:Absorption; D000328:Adult; D001769:Blood / Q000378:metabolism*; D003647:Debrisoquin / Q000378:metabolism*; D005260:Female; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D009883:Ophthalmic Solutions; D011110:Polymorphism, Genetic; D011869:Radioligand Assay; D013999:Timolol / Q000097:blood / Q000493:pharmacokinetics*
D009883:Ophthalmic Solutions; D013999:Timolol; D003647:Debrisoquin