Summary
The inhibitory effects of β-blockers on the metabolism of antipyrine in man and of lignocaine by rat liver microsomes is studied.
In 5 subjects propranolol lowered antipyrine clearance by 37.3 ± 9.9 (SD) %[p < 0.001] compared with control, and metoprolol lowered it by 18.0 ± 4.7 (SD) % [p < 0.01]. Propranolol inhibited the formation of the 3 principal urinary metabolites of antipyrine (i.e. 3-hydroxymethylantipyrine, 4-hydroxyantipyrine and norantipyrine), but there was no evidence of a selective effect on any of these routes.
A strong linear correlation was observed between the degree of inhibition of lignocaine metabolism by rat liver microsomes and the log octanol/buffer pH 7.4 partition coefficient of 13 β-blockers (r2 = 0.84; p < 0.001). This inhibition appeared to be selective for aromatic hydroxylation.
Lignocaine metabolism in microsomes from rats pretreated with propranolol was impaired despite the absence of unchanged propranolol in the preparation. Under these conditions inhibition of lignocaine metabolism may have been caused by a metabolite of propranolol. A clinical case is described in which propranolol probably enhanced the anticoagulant effect of warfarin.
These results may have clinical implications when lipid-soluble β-blockers are prescribed for patients taking other drugs with low therapeutic indices.
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Bax, N.D.S., Lennard, M.S., Al-Asady, S. et al. Inhibition of Drug Metabolism by β-Adrenoceptor Antagonists. Drugs 25 (Suppl 2), 121–126 (1983). https://doi.org/10.2165/00003495-198300252-00036
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DOI: https://doi.org/10.2165/00003495-198300252-00036