title: Timolol metabolism and debrisoquine oxidation polymorphism: a population study.
abstract: 1. The metabolism of orally administered timolol (T) to its ring cleavage ethanolamine (TE) and glycine (TG) products was studied in 108 unrelated hypertensive patients. 2. Statistically significant correlations between the 0-8 h urinary debrisoquine/4-hydroxy-debrisoquine ratio and the T/TE (rs = 0.74, P less than 0.001), T/TG (rs = 0.42, P less than 0.001) and T/TE + TG (rs = 0.49, P less than 0.001) ratios were found. 3. The log10 T/TE, T/TG and T/TE + TG ratios from poor metabolisers of debrisoquine (PMs) were grouped at the upper end of a unimodal distribution. 4. These results indicate that timolol metabolism is partly under monogenic control of the debrisoquine-type. 5. The mean +/- s.d. plasma timolol concentration in PMs (82 +/- 43 ng ml-1) was double that in extensive metabolisers (45 +/- 19 ng ml-1) (P = 0.011). The clinical significance of this observation remains to be established.
authors.affiliation: University Department of Pharmacology and Therapeutics, Royal Hallamshire Hospital, Sheffield.
authors.forename: M S
authors.initials: MS
authors.lastname: Lennard
authors.forename: R V
authors.initials: RV
authors.lastname: Lewis
authors.forename: L A
authors.initials: LA
authors.lastname: Brawn
authors.forename: G T
authors.initials: GT
authors.lastname: Tucker
authors.forename: L E
authors.initials: LE
authors.lastname: Ramsay
authors.forename: P R
authors.initials: PR
authors.lastname: Jackson
authors.forename: H F
authors.initials: HF
authors.lastname: Woods
mesh_terms: D000328:Adult; D003647:Debrisoquin / Q000378:metabolism*; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010641:Phenotype; D013999:Timolol / Q000097:blood / Q000378:metabolism* / Q000652:urine
chemical_list: D007546:Isoquinolines; D013999:Timolol; D003647:Debrisoquin