PMID: 9549640Apr 29, 1998Paper

Protease inhibitors as inhibitors of human cytochromes P450: high risk associated with ritonavir

Journal of Clinical Pharmacology
L L von MoltkeR I Shader

Abstract

Four protease inhibitor antiviral agents (ritonavir, indinavir, nelfinavir, saquinavir) were evaluated as in vitro inhibitors of the activity of six human cytochromes using an in vitro model based on human liver microsomes. Ritonavir was a highly potent inhibitor of P450-3A activity (triazolam hydroxylation), having inhibitory potency slightly less than ketoconazole. Indinavir was also a potent 3A inhibitor, while nelfinavir and saquinavir were less potent. Ritonavir had high inhibition potency against cytochrome P450-2C9 (tolbutamide hydroxylation), -2C19 (S-mephenytoin hydroxylation), and -2D6 (dextromethorphan O-demethylation and desipramine hydroxylation), while the other protease inhibitors had one or more orders of magnitude lower inhibitory activity against these reactions. None of the protease inhibitors had important inhibitory potency against P450-1A2 (phenacetin O-deethylation) or -2E1 (chlorzoxazone hydroxylation). Thus, among available protease inhibitors, ritonavir carries the highest risk of incurring drug interactions due to inhibition of cytochrome P450 activity.

References

Nov 1, 1992·The Journal of Clinical Investigation·J C KolarsP B Watkins
Jun 1, 1996·Journal of Clinical Psychopharmacology·R I ShaderD J Greenblatt
Oct 1, 1996·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·S C PiscitelliH Masur
Jan 8, 1997·JAMA : the Journal of the American Medical Association·S G DeeksJ O Kahn
Apr 1, 1997·Biopharmaceutics & Drug Disposition·M H CourtD J Greenblatt
May 12, 1997·Archives of Internal Medicine·C K McDonald, D R Kuritzkes
Jan 1, 1997·AIDS Clinical Review·S G Deeks, P A Volberding
Feb 12, 1998·British Journal of Clinical Pharmacology·J SchmiderR I Shader
Feb 4, 1998·Biochemical Pharmacology·L L von MoltkeR I Shader
Apr 29, 1998·Journal of Clinical Pharmacology·K VenkatakrishnanR I Shader

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Citations

May 29, 1999·Movement Disorders : Official Journal of the Movement Disorder Society·D Caparros-LefebvreM Strobel
Jan 20, 2005·European Journal of Clinical Pharmacology·Jacques FellayChin B Eap
Jun 8, 2006·European Journal of Clinical Pharmacology·Mikko NiemiJanne T Backman
May 15, 2009·European Journal of Clinical Pharmacology·Julie BertrandUNKNOWN COPHAR2-ANRS 111 Study Group
Feb 15, 2001·Current Infectious Disease Reports·Christopher L. Karp
Sep 11, 2010·Current Osteoporosis Reports·Shitij AroraJameel Iqbal
Feb 22, 2011·European Journal of Drug Metabolism and Pharmacokinetics·Siamak Cyrus KhojastehAnthony Y H Lu
Jun 6, 2000·Advanced Drug Delivery Reviews·J H Lin
Jun 6, 2000·Advanced Drug Delivery Reviews·X Li, W K Chan
Jun 6, 2000·Advanced Drug Delivery Reviews·G C Williams, P J Sinko
Jul 30, 1999·Journal of the American Academy of Dermatology·A K GuptaN H Shear
Aug 28, 1999·Journal of Pharmacological and Toxicological Methods·B W GrandaD J Greenblatt
Dec 14, 1999·Alimentary Pharmacology & Therapeutics·M ToniniF Crema
Aug 10, 2000·British Journal of Clinical Pharmacology·D J Back
Nov 1, 2002·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·C Bradley HareHarry W Lampiris
Jan 30, 2004·AIDS Patient Care and STDs·Jeffrey Nadler
May 27, 2005·AIDS Patient Care and STDs·Benjamin Young
Sep 15, 1999·Anesthesiology·K T OlkkolaP J Neuvonen
Oct 6, 1999·AIDS·G Newshan, P Tsang
Oct 6, 1999·AIDS·M E Hillebrand-HaverkortJ H ten Veen
Oct 6, 2000·Clinical Neuropharmacology·A Berbel GarciaM Toledo Heras
Dec 10, 1999·Journal of Clinical Psychopharmacology·D J GreenblattR I Shader
Aug 13, 2002·Journal of Clinical Psychopharmacology·Scott R PenzakMichael W Jann
Jul 31, 2001·Transplantation·P J GowD Mutimer
Aug 10, 2000·Journal of Acquired Immune Deficiency Syndromes : JAIDS·D J GreenblattR I Shader
Oct 31, 2006·The Pediatric Infectious Disease Journal·Renata Arrington-SandersGeorge K Siberry
Jun 25, 2009·AIDS·Marco BorderiMaria C Re
Feb 3, 2009·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Tamsin A KnoxDavid J Greenblatt
Jan 28, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Feng LiXiaochao Ma
Jul 25, 2007·Antimicrobial Agents and Chemotherapy·Ping LiuAmarnath Sharma
Feb 28, 2001·Journal of Clinical Pharmacology·L L von MoltkeR I Shader
Jul 17, 2001·Journal of Clinical Pharmacology·E StörmerD J Greenblatt
Nov 8, 2001·Journal of Clinical Pharmacology·K VenkatakrishnanD J Greenblatt
Nov 5, 2002·Journal of Clinical Pharmacology·Michael D PerloffDavid J Greenblatt

❮ Previous
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