Abstract
The effect of lopinavir/ritonavir (LPV/r) administration on cytochrome P450 (CYP) enzyme activity was quantified using a phenotyping biomarker cocktail. Changes in CYP2C9, CYP2C19, CYP3A, CYP1A2, N-acetyltransferase-2 (NAT-2), and xanthine oxidase (XO) activities were evaluated using warfarin (WARF) + vitamin K, omeprazole (OMP), intravenous (IV) and oral (PO) midazolam (MDZ), and caffeine (CAF). : Open-label, multiple-dose, pharmacokinetic study in healthy volunteers. Subjects (n = 14) simultaneously received PO WARF 10 mg, vitamin K 10 mg, OMP 40 mg, CAF 2 mg/kg, and IV MDZ 0.025 mg/kg on days (D) 1 and 14, and PO MDZ 5 mg on D2 and D15. LPV/r (400/100 mg twice daily) was administered on D4-17. CYP2C9 and CYP2C19 activities were quantified by S-WARF AUC0-inf and OMP/5-hydroxy OMP ratio, respectively. CYP1A2, NAT-2, and XO activities were quantified by urinary CAF metabolite ratios. Hepatic and intestinal + hepatic CYP3A activities were quantified by IV (CL) and PO (CL/F) MDZ clearance, respectively. After LPV/r therapy, CYP2C9, CYP2C19, and CYP1A2 activity increased by 29%, 100%, and 43% (P = 0.001, 0.046, and 0.001), respectively. No changes were seen in NAT-2 or XO activity. Hepatic and intestinal + hepatic CYP3A activity d...Continue Reading
References
Oct 1, 1992·Clinical Pharmacology and Therapeutics·U Breyer-PfaffP Baumann
Mar 1, 1990·Clinical Pharmacology and Therapeutics·C B EapP Baumann
Apr 1, 1989·Clinical Pharmacology and Therapeutics·L BertilssonT Villén
Jun 1, 1995·Clinical Pharmacology and Therapeutics·J D BalianD A Flockhart
Aug 1, 1996·Clinical Pharmacology and Therapeutics·J S MarinacD A Flockhart
Feb 14, 1997·Toxicology·C IribarneF Berthou
May 1, 1997·Antimicrobial Agents and Chemotherapy·A HsuJ M Leonard
May 15, 1997·The Journal of Clinical Investigation·K S LownP B Watkins
Apr 1, 1996·Pharmacogenetics·U FuhrA H Staib
Mar 7, 1998·British Journal of Clinical Pharmacology·H J FengH H Zhou
Jun 19, 1998·Clinical Pharmacology and Therapeutics·A D KashubaA N Nafziger
Sep 5, 1998·Clinical Pharmacology and Therapeutics·J C GorskiS D Hall
Oct 3, 1998·Clinical Pharmacology and Therapeutics·A D KashubaA N Nafziger
Dec 3, 1998·Antimicrobial Agents and Chemotherapy·H L ShamD W Norbeck
Dec 23, 1998·British Journal of Clinical Pharmacology·N N VachharajaniD S Greene
Jan 7, 1999·The Annals of Pharmacotherapy·K R KnoellE S Cousins
Apr 23, 1999·Pharmaceutical Research·R B KimG R Wilkinson
May 8, 1999·British Journal of Clinical Pharmacology·D J FosterF Bochner
Oct 6, 1999·AIDS·G Newshan, P Tsang
Dec 1, 1999·Clinical Pharmacology and Therapeutics·S M TsunodaD J Greenblatt
Dec 3, 1999·Journal of Clinical Pharmacy and Therapeutics·E Tanaka
Aug 10, 2000·British Journal of Clinical Pharmacology·Y KhaliqD W Cameron
Mar 29, 2001·The New England Journal of Medicine·S C Piscitelli, K D Gallicano
Jul 17, 2001·Journal of Clinical Pharmacology·J S KimJ S Bertino
Jul 28, 2001·Pharmaceutical Research·T SakaiK Okumura
Aug 29, 2001·Clinical Pharmacokinetics·H Takahashi, H Echizen
Mar 27, 2002·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Susan ClarkeDavid J Back
Apr 3, 2002·Pharmacogenetics·Craig R LeeJohn A Pieper
Jun 28, 2002·The Annals of Pharmacotherapy·Amanda H CorbettAngela D M Kashuba
Aug 13, 2002·Journal of Clinical Psychopharmacology·Scott R PenzakMichael W Jann
Aug 22, 2002·Clinical Pharmacology and Therapeutics·Myong-Jin KimAnne N Nafziger
Aug 22, 2002·Clinical Pharmacology and Therapeutics·Junji SaruwatariTakashi Ishizaki
Dec 25, 2002·Antimicrobial Agents and Chemotherapy·Ann HsuEugene Sun
Mar 4, 2003·Biological & Pharmaceutical Bulletin·Tomoko KitaKatsuhiko Okumura
Mar 19, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ajay MadanAndrew Parkinson
Mar 29, 2003·Drugs·Risto S Cvetkovic, Karen L Goa
May 2, 2003·The Journal of Pharmacy and Pharmacology·James L WeemhoffDavid J Greenblatt
May 22, 2003·Drug and Alcohol Dependence·Thomas KostenKishor Gonsai
Aug 7, 2003·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Robert C StevensRichard Bertz
Aug 9, 2003·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Elinore F McCance-KatzPeter Jatlow
Aug 28, 2003·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Ashokkumar B JainJohn J Fung
Oct 31, 2003·AIDS Research and Human Retroviruses·Marta BoffitoGiovanni Di Perri
Oct 31, 2003·Clinical Pharmacology and Therapeutics·Siwaporn ChainuvatiJoseph S Bertino
Nov 25, 2003·Chirality·John G GerberJoseph Gal
Mar 6, 2004·Clinical Pharmacology and Therapeutics·Mary Jayne KennedyGregory L Kearns
Mar 16, 2004·Pharmacogenomics·Takahisa FurutaTakashi Ishizaki
Apr 3, 2004·Journal of Chromatography. a·Hideko KanazawaRyouhei Nishimura
Apr 20, 2004·AIDS·Christoph StephanSchlomo Staszewski
May 12, 2004·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Naser L RezkAngela D M Kashuba
Jul 13, 2004·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Michael L LimAngela D M Kashuba
Citations
Jul 12, 2008·Archives of Toxicology·Olavi PelkonenHannu Raunio
May 7, 2008·European Journal of Clinical Pharmacology·F JosephsonU Diczfalusy
Jun 30, 2009·European Journal of Clinical Pharmacology·Natascia CortiChristiane Pauli-Magnus
Sep 17, 2009·European Journal of Clinical Pharmacology·Julian JenkinsValerie S Kitchen
Aug 11, 2010·European Journal of Clinical Pharmacology·Tuija H NieminenKlaus T Olkkola
Nov 4, 2010·European Journal of Clinical Pharmacology·Dario CattaneoEmilio Clementi
Jul 23, 2013·European Journal of Clinical Pharmacology·Peter N MorcosJonathan Q Tran
Feb 26, 2011·Cancer Chemotherapy and Pharmacology·Keith T FlahertyPeter J O'Dwyer
Mar 2, 2011·Journal of Thrombosis and Thrombolysis·Edith NutescuErika Hellenbart
Feb 10, 2012·The Journal of Antimicrobial Chemotherapy·Pauline Byakika-KibwikaConcepta Merry
Mar 7, 2012·Antimicrobial Agents and Chemotherapy·Mary B WireBin Peng
Aug 19, 2007·CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne·Christine A HughesLilly J Miedzinski
Oct 26, 2013·Clinical Pharmacokinetics·Tony K L KiangMary H H Ensom
Aug 29, 2014·Clinical Pharmacokinetics·Kajal B LarsonEdward P Acosta
Jun 16, 2014·International Journal of Antimicrobial Agents·Birgit S JacobsDavid M Burger
Apr 17, 2013·Journal of Pharmaceutical Sciences·Keizo FukushimaNobuyuki Sugioka
Oct 29, 2013·Enfermedades infecciosas y microbiología clínica·UNKNOWN Panel de expertos de GeSIDA y Plan Nacional sobre el Sida
May 29, 2012·Enfermedades infecciosas y microbiología clínica·UNKNOWN Panel de expertos de Gesida y Plan Nacional sobre el Sida
Aug 5, 2015·Journal of Clinical Pharmacology·David J Greenblatt
Jun 16, 2010·The Veterinary Journal·Yi YangJeffrey F Waring
Jun 18, 2010·Enfermedades infecciosas y microbiología clínica·UNKNOWN Panel de Expertos de Gesida, UNKNOWN Plan Nacional sobre el Sida
Mar 8, 2016·The Journal of Antimicrobial Chemotherapy·Catia MarzoliniDavid Back
Apr 20, 2007·Journal of Clinical Pharmacology·Bradley L UrquhartRichard B Kim
Sep 25, 2008·Journal of Clinical Pharmacology·Martin S Rhee, David J Greenblatt
Jul 20, 2007·The Journal of Pharmacy and Pharmacology·Michael D PerloffDavid J Greenblatt
Aug 21, 2012·Basic & Clinical Pharmacology & Toxicology·Virginie AncrenazJules Desmeules
Apr 11, 2012·Pharmacotherapy·Alice Jenh HsuPaul A Pham
Nov 16, 2010·Journal of Internal Medicine·F Josephson
Feb 26, 2013·Journal of Clinical Pharmacology·Monika Schöller-GyüreRichard M W Hoetelmans
Aug 14, 2010·Journal of Clinical Pharmacology·Fenglei HuangPatrick Robinson
Dec 17, 2009·British Journal of Clinical Pharmacology·David J GreenblattMichael H Court
Oct 30, 2013·Journal of Clinical Pharmacology·Thomas N KakudaRichard M W Hoetelmans
Oct 10, 2014·British Journal of Clinical Pharmacology·Richard M HoglundJoel Tarning
Feb 27, 2015·European Journal of Clinical Investigation·Michele CorrealeDonato Lacedonia
Aug 21, 2014·Journal of Ethnopharmacology·Erica C LarsonMichael R Franklin
Jun 17, 2016·Clinical Pharmacology in Drug Development·Akshanth R PolepallyRajeev M Menon
Jul 2, 2016·Neurotoxicity Research·Ankit ShahAnil Kumar
Feb 9, 2017·Journal of Clinical Pharmacy and Therapeutics·T-Y LiF Liu
Mar 24, 2017·PloS One·Kay SedenSaye H Khoo
Mar 9, 2017·Pharmacotherapy·Spencer H DurhamPatricia Pecora Fulco
Sep 30, 2015·The American Journal of Tropical Medicine and Hygiene·Siwalee RattanapunyaKesara Na-Bangchang
Jan 1, 2011·Pharmaceutics·R Chris Rathbun, Michelle D Liedtke
Jun 19, 2018·The Annals of Pharmacotherapy·Patricia Pecora Fulco, Laura Hill Bannister
Apr 25, 2018·Antimicrobial Agents and Chemotherapy·Felix StaderCatia Marzolini
Oct 16, 2015·Antimicrobial Agents and Chemotherapy·Prajakta S BadriRajeev M Menon
Feb 13, 2019·Journal of Clinical Pharmacology·Scott R Penzak, Carlos Rojas-Fernandez
Aug 5, 2020·The Journal of Antimicrobial Chemotherapy·Catherine HodgeSaye Khoo
Feb 23, 2019·Frontiers in Pediatrics·Nathan John HananBrookie M Best
Aug 14, 2020·Journal of Clinical Medicine·Sweilem B Al RihaniVeronique Michaud
Jun 26, 2020·Journal of Clinical Medicine·Vincenzo RussoGerardo Nigro