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Literature DB >> 6743465

The relationship between debrisoquine oxidation phenotype and the pharmacokinetics and pharmacodynamics of propranolol.

M S Lennard, P R Jackson, S Freestone, G T Tucker, L E Ramsay, H F Woods.

Abstract

The pharmacokinetics and pharmacodynamics of propranolol (80 mg by mouth) were studied in seven extensive and four poor metabolisers of debrisoquine. Evidence for impairment of the 4'-hydroxylation of propranolol was found in poor metabolisers. However, no significant difference was detected in the oral clearance of unchanged drug between the two groups of debrisoquine oxidation phenotypes. Poor metabolisers of debrisoquine did not experience more intense or more prolonged beta-adrenoceptor blockade than extensive metabolisers of debrisoquine.

Entities: Chemical

Mesh：

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Year: 1984 PMID： 6743465 PMCID： PMC1463425 DOI： 10.1111/j.1365-2125.1984.tb02403.x

Source DB: PubMed Journal: Br J Clin Pharmacol ISSN： 0306-5251 Impact factor: 4.335

15 in total

1. Effect of route of administration on the relationship between -adrenergic blockade and plasma propranolol level.

Authors: C R Cleaveland; D G Shand
Journal: Clin Pharmacol Ther Date: 1972 Mar-Apr Impact factor: 6.875

2. Plasma propranolol levels in adults with observations in four children.

Authors: D G Shand; E M Nuckolls; J A Oates
Journal: Clin Pharmacol Ther Date: 1970 Jan-Feb Impact factor: 6.875

3. Defective metabolism of metoprolol in poor hydroxylators of debrisoquine.

Authors: M S Lennard; J H Silas; S Freestone; J Trevethick
Journal: Br J Clin Pharmacol Date: 1982-08 Impact factor: 4.335

4. Defective hydroxylation of bufuralol associated with side-effects of the drug in poor metabolisers.

Authors: P Dayer; A Kubli; A Kupfer; F Courvoisier; L Balant; J Fabre
Journal: Br J Clin Pharmacol Date: 1982-05 Impact factor: 4.335

5. An automated HPLC method for the assay of propranolol and its basic metabolites in plasma and urine.

Authors: M W Lo; B Silber; S Riegelman
Journal: J Chromatogr Sci Date: 1982-03 Impact factor: 1.618

6. Oxidation phenotype--a major determinant of metoprolol metabolism and response.

Authors: M S Lennard; J H Silas; S Freestone; L E Ramsay; G T Tucker; H F Woods
Journal: N Engl J Med Date: 1982-12-16 Impact factor: 91.245

7. Hepatic clearance of drugs. I. Theoretical considerations of a "well-stirred" model and a "parallel tube" model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drug clearance.

Authors: K S Pang; M Rowland
Journal: J Pharmacokinet Biopharm Date: 1977-12

8. Effect of dose and uremia on plasma and urine profiles of propranolol metabolites.

Authors: D W Schneck; J F Pritchard; T P Gibson; J E Vary; A H Hayes
Journal: Clin Pharmacol Ther Date: 1980-06 Impact factor: 6.875

9. Pharmacology of 4-hydroxypropranolol, a metabolite of propranolol.

Authors: J D Fitzgerald; S R O'Donnell
Journal: Br J Pharmacol Date: 1971-09 Impact factor: 8.739

10. Plasma levels of (+) and (-)-propranolol and 4-hydroxypropranolol after administration of racemic (+/-)-propranolol in man.

Authors: C Von Bahr; J Hermansson; K Tawara
Journal: Br J Clin Pharmacol Date: 1982-07 Impact factor: 4.335

22 in total

Review 1. Ethnic differences in drug disposition and responsiveness.

Authors: A J Wood; H H Zhou
Journal: Clin Pharmacokinet Date: 1991-05 Impact factor: 6.447

Review 2. Interethnic differences in drug metabolism: influence of genetic and environmental factors on debrisoquine hydroxylation phenotype.

Authors: A Llerena; J Cobaleda; C Martínez; J Benítez
Journal: Eur J Drug Metab Pharmacokinet Date: 1996 Apr-Jun Impact factor: 2.441

10. Identification of human CYP isoforms involved in the metabolism of propranolol enantiomers--N-desisopropylation is mediated mainly by CYP1A2.

Authors: K Yoshimoto; H Echizen; K Chiba; M Tani; T Ishizaki
Journal: Br J Clin Pharmacol Date: 1995-04 Impact factor: 4.335

The relationship between debrisoquine oxidation phenotype and the pharmacokinetics and pharmacodynamics of propranolol.

1. Effect of route of administration on the relationship between -adrenergic blockade and plasma propranolol level.

2. Plasma propranolol levels in adults with observations in four children.

3. Defective metabolism of metoprolol in poor hydroxylators of debrisoquine.

4. Defective hydroxylation of bufuralol associated with side-effects of the drug in poor metabolisers.

5. An automated HPLC method for the assay of propranolol and its basic metabolites in plasma and urine.

6. Oxidation phenotype--a major determinant of metoprolol metabolism and response.

7. Hepatic clearance of drugs. I. Theoretical considerations of a "well-stirred" model and a "parallel tube" model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drug clearance.

8. Effect of dose and uremia on plasma and urine profiles of propranolol metabolites.

9. Pharmacology of 4-hydroxypropranolol, a metabolite of propranolol.

10. Plasma levels of (+) and (-)-propranolol and 4-hydroxypropranolol after administration of racemic (+/-)-propranolol in man.

Review 1. Ethnic differences in drug disposition and responsiveness.

Review 2. Interethnic differences in drug metabolism: influence of genetic and environmental factors on debrisoquine hydroxylation phenotype.

3. Clinical significance of the sparteine/debrisoquine oxidation polymorphism.

4. Partial metabolic clearances as determinants of the oral bioavailability of propranolol.

5. Polymorphic metabolism of the beta-adrenoreceptor blocking drugs and its clinical relevance.

Review 6. The polymorphic oxidation of beta-adrenoceptor antagonists. Clinical pharmacokinetic considerations.

Review 7. Oxidation phenotype and the metabolism and action of beta-blockers.

Review 8. Clinical significance of genetic influences on cardiovascular drug metabolism.

9. Effect of oxidative polymorphism (debrisoquine/sparteine type) on hepatic first-pass metabolism of bufuralol.

10. Identification of human CYP isoforms involved in the metabolism of propranolol enantiomers--N-desisopropylation is mediated mainly by CYP1A2.