PMID: 75440Feb 25, 1978Paper

Beta-blockade and blood-levels after low-dose oral propranolol: The hepatic "first-pass" threshold revisited

Lancet
R DaviesJ H Laragh

Abstract

Heart-rate, arterial pressure, and plasmarenin activity were determined in six normal subjects at rest and after an injection of 8 microgram isoprenaline with and without prior propranolol administered orally in a dose of 5 mg 8-hourly for a total of five doses. After propranolol, resting heart-rate, systolic pressure, and plasma-renin activity all fell significantly (P less than 0.05 to less than 0.001). When the isoprenaline-induced changes of heart-rate, diastolic pressure, and plasma renin activity without propranolol were compared to those with propranolol, these responses were greatly diminished (P less than 0.01 to less than 0.001). The percent blockade by propranolol of the isoprenaline-induced changes ranged from 65% for diastolic pressure to 77% for heart rate and 78% for plasma-renin activity. Propranolol levels determined by conventional fluorometry were below accurate detection limits, whereas those determined by gas-liquid chromatography ranged from 2.3 to 8.5 ng/ml. These findings, which demonstrate beta-blockade with low-dose propranolol, are not consistent with the existence of a postulated threshold for the hepatic "first-pass effect" in man, which is said to require saturation by single doses of 30 mg or more...Continue Reading

References

Sep 18, 1976·Lancet·R Davies, J D Slater
Jul 1, 1975·Circulation·A S Nies, D G Shand
Oct 19, 1968·Lancet·D R HaddenJ A Weaver
Sep 26, 1973·Journal of Chromatography·E Di SalleP L Morselli

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Citations

Sep 1, 1979·Journal of Neurology, Neurosurgery, and Psychiatry·D JeffersonC D Marsden
Apr 1, 1980·Biopharmaceutics & Drug Disposition·J J MackichanW J Jusko
Aug 1, 1981·Journal of Pharmacokinetics and Biopharmaceutics·L BorgströmR Lenander
Jul 25, 1980·European Journal of Pharmacology·F R Ciofalo

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