Influence of CYP2C19 polymorphism on the pharmacokinetics of nelfinavir and its active metabolite

British Journal of Clinical Pharmacology

Volumn 68, Issue 5, 2009, Pages 682-689

  Damle, Bharat D ^a   Uderman, Howard ^b   Biswas, Pinaki ^a   Crownover, Penelope ^a   Lin, Chang ^b   Glue, Paul ^a  

^a PFIZER INC   (United States)

^b NONE

Author keywords

CYP2C19; M8; Nelfinavir; Pharmacokinetics

Indexed keywords

CYTOCHROME P450 2C19; DRUG METABOLITE; MOXIFLOXACIN; NELFINAVIR; NELFINAVIR HYDROXY TERT BUTYLAMIDE; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DNA POLYMORPHISM; DRUG BLOOD LEVEL; DRUG METABOLISM; FEMALE; GENOTYPE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; MAJOR CLINICAL STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; PHARMACOGENOMICS; PRIORITY JOURNAL; QT INTERVAL; RANDOMIZED CONTROLLED TRIAL; STEADY STATE; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADULT; ARYL HYDROCARBON HYDROXYLASES; FEMALE; HIV PROTEASE INHIBITORS; HUMANS; MALE; METABOLIC CLEARANCE RATE; MIDDLE AGED; NELFINAVIR; POLYMORPHISM, GENETIC; YOUNG ADULT;

EID: 70449341647     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2009.03499.x     Document Type: Article

References (18)

1. Viracept® (nelfinavir mesylate). US Package Insert, Pfizer Inc., July 2007.
2. Perry CM, Frampton JE, McCormack PL, Siddiqui MA, Cvetkovic RS. Nelfinavir: a review of its use in the management of HIV infection. Drugs 2005 65 : 2209 2244.
3. Hirani VN, Raucy JL, Lasker JM. Conversion of the HIV protease inhibitor nelfinavir to a bioactive metabolite by human liver CYP2C19. Drug Metab Dispos 2004 32 : 1462 1467.
4. Zhang KE, Wu E, Patrick AK, Kerr B, Zorbas M, Lankford A, Kobayashi T, Maeda Y, Shetty B, Webber S. Circulating metabolites of the human immunodeficiency virus protease inhibitor nelfinavir in humans: structural identification, levels in plasma, and antiviral activities. Antimicrob Agents Chemother 2001 45 : 1086 1093.
5. Desta Z, Zhao X, Shin J-G, Flockhart DA. Clinical significance of the cytochrome P4502C19 genetic polymorphism. Clin Pharmacokinet 2002 41 : 913 958.
6. Wedlund PJ. The CYP2C19 enzyme polymorphism. Pharmacology 2000 61 : 174 183.
7. Haas DW, Smeaton LM, Shafer RW, Robbins GK, Morse GD, Labbe L, Wilkinson GR, Clifford DB, D'Aquila RT, De Gruttola V, Pollard RB, Merigan TC, Hirsch MS, George AL Jr., Donahue JP, Kim RB. Pharmacogenetics of long-term responses to antiretroviral regimens containing efavirenz and/or nelfinavir: an Adult AIDS Clinical Trials Group Study. J Infect Dis 2005 192 : 1931 1942.
8. Burger DM, Schwietert HR, Colbers EP, Becker M. The effect of the CYP2C19*2 heterozygote genotype on the pharmacokinetics of nelfinavir. Br J Clin Pharmacol 2006 62 : 250 252.
9. Fellay J, Marzolini C, Meaden ER, Back DJ, Buclin T, Chave JP, Decosterd LA, Furrer H, Opravil M, Pantaleo G, Retelska D, Ruiz L, Schinkel AH, Vernazza P, Eap CB, Telenti A, for the Swiss HIV Cohort Study. Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Lancet 2002 359 : 30 6.
10. Hirt D, Mentre F, Tran A, Rey E, Auleley S, Salmon D, Duval X, Treluyer JM, COPHAR2-ANRS Study Group. Effect of CYP2C19 polymorphism on nelfinavir to M8 biotransformation in HIV patients. Br J Clin Pharmacol 2008 65 : 548 557.
11. Saitoh A, Singh KK, Powell CA, Fenton T, Fletcher CV, Brundage R, Starr S, Spector SA. An MDR1-3435 variant is associated with higher plasma nelfinavir levels and more rapid virologic response in HIV-1 infected children. AIDS 2005 19 : 371 380.
12. Damle B, Fosser C, Ito K, Tran A, Clax P, Uderman H, Glue P. Effects of standard and supratherapeutic doses of nelfinavir on cardiac repolarization: a thorough QT study. J Clin Pharmacol 2009 49 : 291 300.
13. E14 Implementation Working Group Questions & Answers. June 4, 2008. Available at http://www.ich.org/LOB/media/MEDIA4719.pdf (last accessed 4 August 2009).
14. Fang AF, Damle BD, LaBadie RR, Crownover PH, Hewlett D Jr., Glue PW. Significant decrease in nelfinavir systemic exposure after omeprazole coadministration in healthy subjects. Pharmacotheraypy 2008 28 : 42 50.
15. Myrand SP, Sekiguchi K, Man MZ, Lin X, Tzeng RY, Teng CH, Hee B, Garrett M, Kikkawa H, Lin CY, Eddy SM, Dostalik J, Mount J, Azuma J, Fujio Y, Jang IJ, Shin IG, Bleavins MR, Williams JA, Paulauskis JD, Wilner K. Pharmacokinetics/ genotype associations for major cytochrome P450 enzymes in native and first- and third-generation Japanese populations: comparison with Korean, Chinese and Caucasian populations. Clin Pharmacol Ther 2008 84 : 347 361.
16. Aweeka F, Motoya T, Thevanayagam L, Blaschke T, Stone J, Jayewardene A, Chi J. Nelfinavir unbound drug interactions and protein binding characteristics. 9th Conference on Retrovirous and Opportunistic Infections. Seattle WA. 2002. [Abstract 448-W DL, Gerber JG. Antiretroviral drug pharmacokinetics in hepatitis with hepatic dysfunction. Clin Infect Dis 2005 40 : 174 181.
17. Regazzi M, Maserati R, Villani P, Cusato M, Zucchi P, Briganti E, Roda R, Sacchelli L, Gatti F, Foglie PD, Nardini G, Fabris P, Mori F, Castelli P, Testa L. Clinical pharmacokinetics of nelfinavir and its metabolite M8 in human immunodeficiency virus (HIV)-positive and HIV-hepatitis C virus-coinfected subjects. Antimicrob Agents Chemother 2005 49 : 643 649.
18. Peytavin G, Landman R, Lamotte C, Trylesinski A, Legac S, Mentre F, Yeni P. Therapeutic drug monitoring of nelfinavir in a prospective study (LIVIR IMEA 014) in HIV-HCV co-infected patients with chronic liver disease). 1st International AIDS Society Conference on HIV Pathogenesis and Treatment; Buenos Aires, Argentina. 2001 [Abstract 349 ].