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Rectal and intravenous propranolol infusion to steady state: Kinetics and β-receptor blockade

1984; Wiley; Volume: 35; Issue: 2 Linguagem: Inglês

10.1038/clpt.1984.20

1532-6535

Leo G. J. de Leede, Carl C. Hug, Simon de Lange, Albertus G. de Boer, D. D. Breimer,

Nausea and vomiting management

Clinical Pharmacology & TherapeuticsVolume 35, Issue 2 p. 148-155 Original Article Rectal and intravenous propranolol infusion to steady state: Kinetics and β-receptor blockade Leo G J de Leede PhD, Corresponding Author Leo G J de Leede PhD Department of Pharmaceutical Technology and Biopharmacy Department of Pharmacology Department of Anesthesiology, University of LeidenLeo G J de Leede, Department of Pharmaceutical Technology and Biopharmacy, University of Leiden, Gorlaeus Labs., P.O. Box 9502, 2300 RA Leiden, The Netherlands.Search for more papers by this authorCarl C Hug Jr. MD, PhD, Carl C Hug Jr. MD, PhD Department of Pharmaceutical Technology and Biopharmacy Department of Pharmacology Department of Anesthesiology, University of LeidenSearch for more papers by this authorSimon de Lange MD, PhD, Simon de Lange MD, PhD Department of Pharmaceutical Technology and Biopharmacy Department of Pharmacology Department of Anesthesiology, University of LeidenSearch for more papers by this authorAlbertus G de Boer PhD, Albertus G de Boer PhD Department of Pharmaceutical Technology and Biopharmacy Department of Pharmacology Department of Anesthesiology, University of LeidenSearch for more papers by this authorDouwe D Breimer PhD, Douwe D Breimer PhD Department of Pharmaceutical Technology and Biopharmacy Department of Pharmacology Department of Anesthesiology, University of LeidenSearch for more papers by this author Leo G J de Leede PhD, Corresponding Author Leo G J de Leede PhD Department of Pharmaceutical Technology and Biopharmacy Department of Pharmacology Department of Anesthesiology, University of LeidenLeo G J de Leede, Department of Pharmaceutical Technology and Biopharmacy, University of Leiden, Gorlaeus Labs., P.O. Box 9502, 2300 RA Leiden, The Netherlands.Search for more papers by this authorCarl C Hug Jr. MD, PhD, Carl C Hug Jr. MD, PhD Department of Pharmaceutical Technology and Biopharmacy Department of Pharmacology Department of Anesthesiology, University of LeidenSearch for more papers by this authorSimon de Lange MD, PhD, Simon de Lange MD, PhD Department of Pharmaceutical Technology and Biopharmacy Department of Pharmacology Department of Anesthesiology, University of LeidenSearch for more papers by this authorAlbertus G de Boer PhD, Albertus G de Boer PhD Department of Pharmaceutical Technology and Biopharmacy Department of Pharmacology Department of Anesthesiology, University of LeidenSearch for more papers by this authorDouwe D Breimer PhD, Douwe D Breimer PhD Department of Pharmaceutical Technology and Biopharmacy Department of Pharmacology Department of Anesthesiology, University of LeidenSearch for more papers by this author First published: February 1984 https://doi.org/10.1038/clpt.1984.20Citations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract The effects of intravenous propranolol infusion for 24 hr was compared with those of zero-order rectal administration by an osmotic delivery system in six healthy subjects. In plasma and urine, levels of propranolol, 4-OH-propranolol (4-OH-P), and conjugates were determined just before and at 6 hr and at 20 hr during drug administration. With the rectally applied osmotic delivery system providing zero-order release, fairly constant steady-state levels of propranolol in plasma were produced within 12 to 15 hr (four to five times elimination t½). The mean steady-state levels were 25 ng/ml after 1.1 µg/min/kg rectally and 60 ng/ml after 0.8 µg/min/kg IV. The mean rectal systemic availability was 33%; the elimination t½s for the two routes did not differ. The results of analysis of plasma for metabolites indicate that after rectal propranolol different metabolic pathways are followed and that there is partial avoidance of first-pass elimination. The isoproterenol challenge resulted in a reproducible assessment of β-receptor blockade that was closely related to the propranolol concentration in plasma in all subjects and for both routes of administration. With rate-controlled release of propranolol from an osmotic delivery device, the rectal route provides an alternative to intravenous infusion to achieve constant steady-state propranolol concentrations. This may be useful for research purposes or during the perioperative period in surgical patients. Clinical Pharmacology and Therapeutics (1984) 35, 148–155; doi:10.1038/clpt.1984.20 Citing Literature Volume35, Issue2February 1984Pages 148-155 RelatedInformation