Do beta blockers differ in their effects on hepatic microsomal enzymes and liver blood flow?
The effects of three beta blockers on liver blood flow and hepatic enzyme activity were investigated. Eight healthy subjects received placebo, 100 mg metoprolol, 40 mg nadolol, and 60 mg propranolol orally three times a day for four days in a randomized block design. On the fourth day of each treatment, beta blockade was measured by inhibition of exercise-induced tachycardia and apparent liver blood flow was measured by indocyanine green clearance. Plasma concentrations of the beta blockers were measured 2 hours after the early morning dose. Metoprolol produced the greatest inhibition of exercise tachycardia. All three drugs appeared to reduce liver blood flow, but this was only statistically significant in the case of propranolol. Enzyme inhibition occurred but to a varying extent. Propranolol produced a 36 per cent fall in antipyrine clearance (P less than 0.1) while metoprolol and nadolol both caused a 12 per cent reduction (P less than 0.05 and P = 0.06, respectively). Wide interindividual variation in the plasma concentrations of the drugs limit interpretation, but the results suggest that at the doses used, metoprolol and nadolol may be less likely to cause significant drug interaction by enzyme inhibition than propranolol.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000983:Antipyrine / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007208:Indocyanine Green; D007700:Kinetics; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D009248:Nadolol; D005082:Physical Exertion / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D009248:Nadolol; D011433:Propranolol; D008790:Metoprolol; D007208:Indocyanine Green; D000983:Antipyrine