Timolol metabolism and debrisoquine oxidation polymorphism: a population study.
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.
Lennard
M S
MS
University Department of Pharmacology and Therapeutics, Royal Hallamshire Hospital, Sheffield.
Lewis
R V
RV
Brawn
L A
LA
Tucker
G T
GT
Ramsay
L E
LE
Jackson
P R
PR
Woods
H F
HF
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
D007546:Isoquinolines; D013999:Timolol; D003647:Debrisoquin