Literature DB >> 11122720

Does differing metabolism by cytochrome p450 have clinical importance?

M H Davidson1.   

Abstract

The cytochrome P450 (CYP) is a group of enzymes that oxidatively modify drugs to a more water-soluble form for renal excretion. Nearly 50% of all clinically used medications and endogenous steroids are metabolized by the CYP enzyme 3A4, which explains why many of the important potential drug interactions involved this enzyme. Despite an excellent safety record, CYP 3A4 statins (lovastatin, simvastatin, atorvastatin) taken concomitantly with a potent CYP 3A4 inhibitor may increase the risk for adverse events (myopathy, rhabdomyolysis). This article describes the clinical significance of CYP metabolism as the pathways relate to the use of statins, including brief discussions on statins, fibrates, cyclosporine, and calcium channel blockers. In light of these potential interactions, continued vigilance by physicians is necessary to ensure the safe use of statins.

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Year:  2000        PMID: 11122720     DOI: 10.1007/s11883-000-0090-4

Source DB:  PubMed          Journal:  Curr Atheroscler Rep        ISSN: 1523-3804            Impact factor:   5.113


  31 in total

1.  Rhabdomyolysis and renal failure associated with cerivastatin-gemfibrozil combination therapy.

Authors:  G W Pogson; L H Kindred; B G Carper
Journal:  Am J Cardiol       Date:  1999-04-01       Impact factor: 2.778

2.  Lovastatin and rhabdomyolysis.

Authors:  J Z Ayanian; C S Fuchs; R M Stone
Journal:  Ann Intern Med       Date:  1988-10-15       Impact factor: 25.391

3.  Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole.

Authors:  P J Neuvonen; T Kantola; K T Kivistö
Journal:  Clin Pharmacol Ther       Date:  1998-03       Impact factor: 6.875

4.  Accumulation of lovastatin, but not pravastatin, in the blood of cyclosporine-treated kidney graft patients after multiple doses.

Authors:  C Olbricht; C Wanner; T Eisenhauer; V Kliem; R Doll; M Boddaert; P O'Grady; M Krekler; B Mangold; U Christians
Journal:  Clin Pharmacol Ther       Date:  1997-09       Impact factor: 6.875

5.  Concomitant use of cytochrome P450 3A4 inhibitors and simvastatin.

Authors:  P J Gruer; J M Vega; M F Mercuri; M R Dobrinska; J A Tobert
Journal:  Am J Cardiol       Date:  1999-10-01       Impact factor: 2.778

6.  Cholesterol-lowering therapy after heart transplantation: a 12-month randomized trial.

Authors:  P W Pflugfelder; M Huff; R Oskalns; L Rudas; W J Kostuk
Journal:  J Heart Lung Transplant       Date:  1995 Jul-Aug       Impact factor: 10.247

7.  The fate of naringin in humans: a key to grapefruit juice-drug interactions?

Authors:  U Fuhr; A L Kummert
Journal:  Clin Pharmacol Ther       Date:  1995-10       Impact factor: 6.875

Review 8.  Rational assessment of the interaction profile of cerivastatin supports its low propensity for drug interactions.

Authors:  W Mück
Journal:  Drugs       Date:  1998       Impact factor: 9.546

9.  QT interval prolongation and torsades de pointes due to erythromycin lactobionate.

Authors:  K C Oberg; J L Bauman
Journal:  Pharmacotherapy       Date:  1995 Nov-Dec       Impact factor: 4.705

10.  Interaction between grapefruit juice and midazolam in humans.

Authors:  H H Kupferschmidt; H R Ha; W H Ziegler; P J Meier; S Krähenbühl
Journal:  Clin Pharmacol Ther       Date:  1995-07       Impact factor: 6.875

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  9 in total

1.  Transdermal application of lovastatin to rats causes profound increases in bone formation and plasma concentrations.

Authors:  G E Gutierrez; D Lalka; I R Garrett; G Rossini; G R Mundy
Journal:  Osteoporos Int       Date:  2006-05-03       Impact factor: 4.507

2.  [Pharmacological interactions of statins].

Authors:  J M Alvarez Gutiérrez; J D López-Torres Hidalgo; P Galdón Blesa; E M García Ruiz; F Naharro de Mora
Journal:  Aten Primaria       Date:  2003-03-15       Impact factor: 1.137

Review 3.  Management of hypercholesterolaemia in postmenopausal women.

Authors:  Michael H Davidson; Kevin C Maki; Sherry Katz Karp; Kate A Ingram
Journal:  Drugs Aging       Date:  2002       Impact factor: 3.923

4.  CYP2C9 and 3A4 play opposing roles in bioactivation and detoxification of diphenylamine NSAIDs.

Authors:  Mary Alexandra Schleiff; Samantha Crosby; Madison Blue; Benjamin Mark Schleiff; Gunnar Boysen; Grover Paul Miller
Journal:  Biochem Pharmacol       Date:  2021-11-05       Impact factor: 5.858

Review 5.  Statins and myotoxicity.

Authors:  John A Farmer
Journal:  Curr Atheroscler Rep       Date:  2003-03       Impact factor: 5.113

Review 6.  Clinically important drug interactions with intravenous anaesthetics in older patients.

Authors:  Helge Eilers; Claus Niemann
Journal:  Drugs Aging       Date:  2003       Impact factor: 3.923

Review 7.  Effects of HMG-CoA reductase inhibitors on skeletal muscle: are all statins the same?

Authors:  Marc Evans; Alan Rees
Journal:  Drug Saf       Date:  2002       Impact factor: 5.606

Review 8.  Combination lipid-lowering therapy in diabetes.

Authors:  Michael H Davidson
Journal:  Curr Diab Rep       Date:  2003-06       Impact factor: 4.810

Review 9.  Calcium channel blocker class heterogeneity: select aspects of pharmacokinetics and pharmacodynamics.

Authors:  Domenic A Sica
Journal:  J Clin Hypertens (Greenwich)       Date:  2005-04       Impact factor: 3.738

  9 in total

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