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Selectivity and dose‐dependency of the inhibitory effect of propranolol on theophylline metabolism in man.
Author(s) -
Miners JO,
Wing LM,
Lillywhite KJ,
Robson RA
Publication year - 1985
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1985.tb05064.x
Subject(s) - theophylline , hydroxylation , metabolite , propranolol , chemistry , demethylation , pharmacology , metabolism , pharmacokinetics , medicine , endocrinology , biochemistry , enzyme , gene expression , dna methylation , gene
The effects of separate 5 day pretreatments of propranolol 120 mg day‐1 and 720 mg day‐1 on theophylline clearance and metabolism at steady‐ state were determined in seven healthy males. Propranolol 120 mg day‐1 decreased theophylline plasma clearance (CL) by 30%. Clearance of theophylline to each metabolite was reduced by this treatment, clearances to the two demethylated products by 42‐43% and clearance to the 8‐hydroxylation product by 27%. Propranolol 720 mg day‐1 decreased theophylline CL by 52%. Again, clearance of theophylline to each metabolite was reduced by this treatment, clearances to the two demethylation products by 73‐77% and clearance to the 8‐hydroxylation product by 44%. These data are consistent with a dose‐dependent and selective inhibitory effect of propranolol on the separate forms of cytochrome P‐450 involved in theophylline demethylation and 8‐ hydroxylation.