Affordable Access

Pharmacokinetics and beta-blocking effects of timolol in poor and extensive metabolizers of debrisoquin.

Authors
  • McGourty, J C
  • Silas, J H
  • Fleming, J J
  • McBurney, A
  • Ward, J W
Type
Published Article
Journal
Clinical pharmacology and therapeutics
Publication Date
Oct 01, 1985
Volume
38
Issue
4
Pages
409–413
Identifiers
PMID: 2864157
Source
Medline
License
Unknown

Abstract

We studied the pharmacokinetics and beta-blocking effects of a single, oral 20 mg dose of timolol in six poor metabolizers (PMs) and six extensive metabolizers (EMs) of debrisoquin. The plasma timolol concentration was significantly higher in PMs than in EMs. There was a fourfold difference in mean AUC (1590 +/- 1133 vs. 394 +/- 239 ng X hr/ml; P less than 0.01) and a twofold difference in mean t1/2 (7.5 +/- 3 vs. 3.7 +/- 1.7 hours; P less than 0.01), reflecting differences in oral clearance (13.1 +/- 7.8 vs. 48.5 +/- 23.2 L/hr; P less than 0.01). The degree of beta-blockade was greater in PMs than in EMs at 12 hours (30.9% vs. 18.2%; P less than 0.05) and at 24 hours (28.3% vs. 13.1%; P less than 0.05). In the group as a whole the metabolic ratio correlated positively with both kinetic data and beta-blockade, but some overlap was observed. Hence timolol metabolism appears to be subject to debrisoquin-type polymorphism, which results in interphenotypic variation in plasma concentration and beta-blocking effect.

Report this publication

Statistics

Seen <100 times