Pharmacokinetics of nelfinavir in subjects with hepatic impairment

Journal of Clinical Pharmacology

Volumn 46, Issue 11, 2006, Pages 1241-1249

  Damle, Bharat ^a   Hewlett Jr , Dial ^a   Hsyu, Poe Hirr ^b   Becker, Mark ^b   Petersen, Annkatrin ^b  

^a PFIZER INC   (United States)

^b Mail Stop 685/19/08 ^*

Author keywords

Hepatic function; M8; Nelfinavir; Pharmacokinetics

Indexed keywords

ASPARTATE AMINOTRANSFERASE; DRUG METABOLITE; NELFINAVIR; PLASMA PROTEIN;

ADULT; AREA UNDER THE CURVE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BLOOD SAMPLING; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DISEASE SEVERITY; DRUG ACCUMULATION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DOSE REGIMEN; DRUG EFFECT; DRUG EXPOSURE; DRUG HALF LIFE; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG TOLERABILITY; EVALUATION; FEMALE; HUMAN; LEUKOPENIA; LIVER DISEASE; LIVER DYSFUNCTION; MALE; OPEN STUDY; PARALLEL DESIGN; STEADY STATE;

ADULT; AREA UNDER CURVE; FEMALE; HALF-LIFE; HEPATIC INSUFFICIENCY; HIV PROTEASE INHIBITORS; HUMANS; MALE; MIDDLE AGED; NELFINAVIR;

EID: 33749868989     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270006292164     Document Type: Article

References (24)

1. Sulkowski MS, Mast EE, Seeff LB, Thomas DL. Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus. Clin Infect Dis. 2000;30:S77-S84.
2. Soriano V, Kirk O, Antunes F, et al. The influence of hepatitis C virus (HCV) on the prognosis of HIV-infected persons: the EuroSIDA Study. In: 13th International AIDS Conference; July 9-14, 2000; Durban, South Africa. Abstract ThOrB655.
3. Rodighiero V. Effects of liver disease on pharmacokinetics: an update. Clin Pharmacokinet. 1999;37:399-431.
4. Kaldor SW, Kalish VJ, Davies JF II, et al. Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease. J Med Chem. 1997;40:3979-3985.
5. Patick AK, Mo H, Markowitz M, et al. Antiviral and resistance studies of AG1343, an orally bioavailable inhibitor of human immunodeficiency virus protease. Antimicrob Agents Chemother. 1996;40:292-297.
6. Viracept (nelfinavir) [product information]. New York, NY: Agouron Pharmaceuticals Inc; 2004. Available at: http://www.viracept.com/pdf/ prescribinginformation.pdf. Accessed March 9, 2006.
7. 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.
8. Jackson KA, Rosenbaum SE, Kerr BM. A population pharmacokinetic analysis of nelfinavir mesylate in human immunodeficiency virus-infected patients enrolled in a phase III clinical trial. Antimicrob Agents Chemother. 2000;44:1832-1837.
9. Zhang KE, Wu E, Patick AK, et al. 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.
10. Khaliq Y, Gallicano K, Seguin I, et al. Single and multiple dose pharmacokinetics of nelfinavir and CYP2C19 activity in human immunodeficiency virus-infected patients with chronic liver disease. Br J Clin Pharmacol. 2000;50:108-115.
11. Lillibridge JH, Lee CA, Pithavala YK, et al. The role of polymorphic CYP2C19 in the metabolism of nelfinavir mesylate. In: 5th International ISSX (International Society for the Study of Xenobiotics) Meeting; October 25-29, 1998; Cairns, Australia. Abstract 1156.
12. US Department of Health and Human Services (DHHS). Guidance for industry: pharmacokinetics in patients with impaired hepatic function. Available at: www.fda.gov/cder/guidance/3625fnl.htm. Accessed June 13, 2006.
13. Regazzi M, Maserati R, Villani P, et al. 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.
14. Maserati R, Villani P, Seminari E, Pan A, Lo Caputo S, Regazzi MB. High plasma levels of nelfinavir and efavirenz in two HIV-positive patients with hepatic disease. AIDS. 1999;13:870-871.
15. Robertson SM, Scarsi KK, Postelnick MJ, Lynch P. Elevated plasma concentrations of protease inhibitors and nonnucleoside reverse transcriptase inhibitors in patients coinfected with human immunodeficiency virus and hepatitis B or C: case series and literature review. Pharmacotherapy. 2005;25:1068-1072.
16. Adedoyin A, Arns PA, Richards WO, Wilkinson GR, Branch RA. Selective effect of liver disease on the activities of specific metabolizing enzymes: investigation of cytochromes P450 2C19 and 2D6. Clin Pharmacol Ther. 1998;64:8-17.
17. Wyles DL, Gerber JG. Antiretroviral drug pharmacokinetics in hepatitis with hepatic dysfunction. Clin Infect Dis. 2005;40:174-181.
18. Peytavin G, Landman R, Lamotte C, et al. Therapeutic drug monitoring of nelfinavir in a prospective study in HIV-HCV coinfected patients with chronic liver disease. In: 1st International AIDS Society Conference on HIV Pathogenesis and Treatment; 2001; Buenos Aires, Argentina. Abstract 349.
19. Hsyu PH, Lewis RH, Tran JQ, Lillibridge JH, Smith MD, Kerr BM. Pharmacokinetics (PK) of nelfinavir (NFV) after once daily dosing in combination with mini-doses of ritonavir (RTV) in healthy subjects. In: 13th International AIDS Conference; July 9-14, 2000; Durban, South Africa. Abstract LbPeB7049.
20. Bruno R, Sacchi P, Maiocchi L, Zocchetti C, Filice G. Hepatotoxicity and nelfinavir: a meta-analysis. Clin Gastroenterol Hepatol. 2005;3:482-488.
21. Poizot-Martin I, Marimoutou C, Drogoul-Vey MP, et al. Nelfinavir in HIV-HCV coinfected patients: a 24-month follow-up in a cohort of 82 patients. AIDS Res Human Retroviruses. 2005;21:841-844.
22. Rotger M, Taffé E, Bleiber G, et al. Gilbert syndrome and the development of antiretroviral therapy-associated hyperbilirubinemia. J Infect Dis. 2005;192:1381-1386.
23. Scherpbier H, Bekker V, van Leth F, Jurriaans S, Lange JMA, Kuijpers TW. Long-term experience with combination antiretroviral therapy that contains nelfinavir for up to 7 years in a pediatric cohort. Pediatrics. 2006;117:528-536.
24. Acosta E, Gerber J, Adult Pharmacology Group of ACTG. Position paper on therapeutic drug monitoring of antiretroviral agents. AIDS Res Human Retroviruses. 2002;18:825-834.