N-acetyltransferase: the practical consequences of polymorphic activity in man

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Stephen C Mitchell

Abstract

Over the years, numerous studies have supported the premise that individuals possessing the "slow acetylator" phenotype are more at risk from developing drug side-effects. Most prominent amongst these reports are those concerned with hepatotoxicity and peripheral neuropathy following treatment with isoniazid, lupus-like symptoms during procainamide therapy and experiencing hypersensitivity reactions to the various sulphonamide derivatives. Similarly, "slow acetylators" undergoing heavy exposure to arylamines and related carcinogens are more likely to develop bladder cancer. Contrariwise, there appears a slight risk of "rapid acetylators" developing pancreatic tumours.Other therapeutic agents for which polymorphic N-acetylation plays a minor role in their metabolism have been investigated but any impact of this metabolic difference on clinical efficacy or associated toxicity is still under question. In the search for clues as to the underlying aetiology, patient groups with many disease states have been examined for association with differences in N-acetylation and the majority have provided data that could be interpreted as equivocal. Studies have given contradictory, often opposing, results, calculated risk factors that are (p...Continue Reading

References

Dec 1, 1975·Australian and New Zealand Journal of Medicine·S N Hunyor
Aug 1, 1978·European Journal of Clinical Investigation·R PlatzerR Preisig
Feb 28, 1979·Psychopharmacology·W J TilstoneE C Johnstone
Nov 1, 1975·Clinical Pharmacology and Therapeutics·K M Das, M A Eastwood
Apr 1, 1977·Arthritis and Rheumatism·B FoadE V Hess
Sep 1, 1978·British Journal of Clinical Pharmacology·E F MarshallM Roth
Apr 1, 1979·Annals of the Rheumatic Diseases·D H LawsonA Solomon
Oct 1, 1979·Biopharmaceutics & Drug Disposition·A R WallerD A O'Kelly
Jan 1, 1978·Oncology·L N BulovskayaM V Pavlova
Feb 1, 1976·Journal of Medical Genetics·A K Karim, D A EVANS
Oct 1, 1977·British Journal of Clinical Pharmacology·D H Lawson, H Jick
Apr 1, 1976·Journal of Pharmacokinetics and Biopharmaceutics·G A Ellard, P T Gammon
Jan 1, 1976·Acta Medica Scandinavica·I StrandbergF Sjöqvist
Apr 1, 1975·Clinical Pharmacology and Therapeutics·T P GibsonW A Briggs
Apr 1, 1975·Acta Medica Scandinavica·E Karlsson, L Molin
Jul 1, 1975·Clinical Pharmacology and Therapeutics·J R MitchellH R Keiser
Feb 1, 1991·Chest·M A SteeleR M DesPrez
Nov 1, 1991·Clinical Pharmacology and Therapeutics·M J RatainJ Smiddy
Oct 1, 1991·British Journal of Clinical Pharmacology·W SiegmundR Wulkow
Jan 1, 1991·Clinical Pharmacology and Therapeutics·M J RiederS P Spielberg
Dec 1, 1990·Clinical Pharmacology and Therapeutics·D G MayR A Branch
Jul 15, 1990·International Journal of Cancer. Journal International Du Cancer·J C WohllebN P Lang
Sep 1, 1989·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·R SaezT J Melink
Oct 1, 1989·British Journal of Clinical Pharmacology·M D ColemanB K Park
Jan 1, 1989·International Journal of Dermatology·G Wozel
Dec 1, 1985·Annals of the Rheumatic Diseases·T PullarH A Capell
Mar 1, 1988·Carcinogenesis·P A PhilipH J Rogers
Nov 1, 1987·European Journal of Cancer & Clinical Oncology·P A PhilipR A Cartwright
Oct 1, 1986·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·J W Gorrod, D Manson
Jan 1, 1987·Cancer Chemotherapy and Pharmacology·P A PhilipP G Harper
Jan 1, 1987·Oncology·J M LaderoG Pérez-Manga
Nov 1, 1986·Archives of Surgery·N P LangF F Kadlubar
Mar 1, 1986·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·T YamamotoC Hirayama
Mar 17, 1973·Lancet·E C Johnstone, W Marsh
Jan 1, 1973·Drug Metabolism Reviews·A R Jones
Jul 1, 1972·Clinical Pharmacology and Therapeutics·H Schröder, D E Campbell
Mar 1, 1972·Journal of Medical Genetics·D A EVANSJ M Vetters
May 1, 1972·Clinical Pharmacology and Therapeutics·R Zacest, J Koch-Weser
Mar 1, 1983·Environmental Health Perspectives·C M King, I B Glowinski
Feb 1, 1983·Journal of Medical Genetics·A K Azad KhanS C Truelove
May 1, 1983·Clinical Pharmacology and Therapeutics·A J AtkinsonM J Nevin
Jan 1, 1983·European Journal of Clinical Pharmacology·P YlitaloT Metsä-Ketelä
Oct 1, 1984·The Journal of Allergy and Clinical Immunology·E M Tan, R L Rubin
Dec 1, 1983·Journal of Epidemiology and Community Health·R A CartwrightD Barham-Hall
Jan 1, 1984·European Journal of Clinical Pharmacology·L E RamsayS Freestone
Sep 1, 1982·The British Journal of Psychiatry : the Journal of Mental Science·E S PaykelR R Parker
Apr 1, 1980·The British Journal of Psychiatry : the Journal of Mental Science·P TyrerM Whitford
May 1, 1982·British Journal of Clinical Pharmacology·M J VandenburgR A Ahmad
Jun 1, 1982·Diabetologia·G M ShenfieldR Tjokresetio
Sep 1, 1982·British Journal of Cancer·R C CoombesE C Nice
Jan 1, 1982·European Journal of Clinical Pharmacology·P A ReeceR Zacest
Sep 1, 1981·Clinical Pharmacology and Therapeutics·M E MillerR H Levy
Jan 1, 1981·Scandinavian Journal of Rheumatology·I LedenE Wàhlin-Boll
Dec 1, 1981·Annals of the Rheumatic Diseases·C Kelly, I D Griffiths
May 1, 1980·Arthritis and Rheumatism·M M ReidenbergW C Robbins
Dec 1, 1980·Clinical Pharmacology and Therapeutics·P A ReeceR Zacest
Mar 1, 1995·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M J RatainR L Schilsky
Oct 1, 1994·Environmental Health Perspectives·S J Land, C M King
Jan 1, 1993·Fundamental & Clinical Pharmacology·E J SereeY A Barra
Jul 1, 1996·Clinical Pharmacology and Therapeutics·G R KaufmannW E Haefeli
Feb 1, 1996·Pharmacogenetics·V VlahovA Michailova
May 1, 1997·American Journal of Respiratory and Critical Care Medicine·D P ParkinP P van Jaarsveld
May 12, 1997·Mutation Research·J S FeltonR W Wu
Dec 31, 1997·British Journal of Rheumatology·I GunnarssonB Ringertz
Jan 20, 1998·Clinical Pharmacology and Therapeutics·E ZielińskaG Rebowski
Sep 16, 1998·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·K I SkogM I Jägerstad
May 26, 1999·Clinical Pharmacology and Therapeutics·B Gawrońska-SzklarzG Kurzawski
Aug 21, 2001·Journal of the American Academy of Dermatology·Y I Zhu, M J Stiller
Mar 27, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yi-Shin HuangShou-Dong Lee
Jun 5, 2002·Journal of Clinical Pharmacology·William M O'NeilCraig K Svensson
Dec 21, 2002·British Journal of Clinical Pharmacology·Muradiye NacakIvar Roots
Jan 18, 2003·American Journal of Respiratory and Critical Care Medicine·Marc WeinerTuberculosis Trials Consortium
Jul 1, 1961·British Heart Journal·P C REYNELL
Aug 13, 1960·British Medical Journal·D A EVANSV A McKUSICK
Nov 10, 1961·Science·S SUNAHARA OGAWAM
Mar 23, 2004·Pharmaceutical Research·Shunichi KumagaiKatsuhiko Okumura
Feb 9, 2005·International Journal of Cancer. Journal International Du Cancer·Andrew T ChanCharles S Fuchs
Apr 28, 2005·Antimicrobial Agents and Chemotherapy·Martina Kinzig-SchippersUwe Fuhr
Nov 1, 2005·Drug Metabolism Reviews·Sotiria Boukouvala, Giannoulis Fakis
Jul 13, 2006·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Frederica P PereraDouglas A Bell
Sep 2, 2006·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Eveline Jaquenoud SirotPierre Baumann
Jul 28, 2007·The Journal of Biological Chemistry·Hong WuAlexander N Plotnikov
Feb 1, 1992·British Heart Journal·A Hollman
Nov 14, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Katsuhiko MizunoTsuyoshi Yokoi
Jul 20, 2010·Archives of Medical Research·Xu ZhongLuo Na
Oct 5, 2010·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Crisiane Wais ZanrossoMaria S Pombo-de-Oliveira
Feb 5, 2011·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Dan CuiWeiquan Lu
Jan 21, 2012·The Journal of Pharmacology and Experimental Therapeutics·Manna TemesváriKatalin Monostory
Jul 31, 2012·Pharmacogenomics·Rashmi R Shah, Robert L Smith
Feb 27, 2013·Nature Reviews. Rheumatology·Aleksander M Grabiec, Kris A Reedquist
Jun 11, 2014·British Journal of Clinical Pharmacology·Rashmi R Shah, Robert L Smith
Jun 26, 2015·Pharmacogenetics and Genomics·Elena García-MartínJosé A G Agúndez
Sep 18, 2016·The International Journal of Neuropsychopharmacology·Katalin TóthKatalin Monostory
Mar 25, 2017·The International Journal of Neuropsychopharmacology·Katalin TóthKatalin Monostory
Jun 14, 2017·Biochemical Pharmacology·Keigo KonishiMiki Nakajima
Jul 12, 2018·BioMed Research International·Recep Dursunİlknur Çınar
Mar 27, 2019·European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)·Sanjeev BudhathokiShoichiro Tsugane

Citations

Oct 24, 2020·Expert Opinion on Drug Metabolism & Toxicology·David W Hein, Lori M Millner

Related Concepts

NAT2 protein, human
Acetylation
Arylamine N-Acetyltransferase
Tubazide
Genetic Polymorphism
Malignant Neoplasm of Urinary Bladder
Carcinogens
Hypersensitivity
Isoniazid
Metabolism

Related Feeds

Antitubercular Agents (ASM)

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.

Antitubercular Agents

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.