Ritonavir greatly impairs CYP3A activity in HIV infection with chronic viral hepatitis

Journal of Acquired Immune Deficiency Syndromes

Volumn 49, Issue 4, 2008, Pages 358-368

  Knox, Tamsin A ^a,b   Oleson, Lauren ^a   Von Moltke, Lisa L ^a   Kaufman, Rhonda C ^a   Wanke, Christine A ^a   Greenblatt, David J ^a  

^a TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b TUFTS MEDICAL CENTER   (United States)

Author keywords

Chronic hepatitis; CYP3A; HIV; Ritonavir

Indexed keywords

AMPRENAVIR PHOSPHATE; ATAZANAVIR; CYTOCHROME P450 3A; EFAVIRENZ; KETOCONAZOLE; LOPINAVIR PLUS RITONAVIR; MIDAZOLAM; PHENYTOIN; PROTEINASE INHIBITOR; RITONAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR;

ADULT; ARTICLE; CHRONIC HEPATITIS; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG EXPOSURE; DRUG HALF LIFE; HEPATITIS C; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LIVER CLEARANCE; MALE; MIXED INFECTION; MORNING DOSAGE; PRIORITY JOURNAL; PROTEIN EXPRESSION;

ADMINISTRATION, ORAL; ADULT; CYTOCHROME P-450 ENZYME SYSTEM; DRUG INTERACTIONS; GABA MODULATORS; HEPATITIS B, CHRONIC; HEPATITIS C, CHRONIC; HIV INFECTIONS; HIV PROTEASE INHIBITORS; HUMANS; INJECTIONS, INTRAVENOUS; MALE; MIDAZOLAM; MIDDLE AGED; RITONAVIR;

EID: 57649136624     PISSN: 15254135     EISSN: None     Source Type: Journal    
DOI: 10.1097/QAI.0b013e31818c7efe     Document Type: Article

References (85)

1. Dieterich DT. Hepatitis C virus and human immunodeficiency virus: clinical issues in coinfection. Am J Med. 1999;107 (6B):27.
2. Sulkowski MS, Thomas DL. Hepatitis C in the HIV-infected person. Ann Intern Med. 2003;138:197-207.
3. Benhamou Y, Bochet M, Di Martino y et al. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group. Hepatology. 1999;30:1054-1058.
4. Housset C, Pol S, Carnot F, et al. Interactions between human immunodeficiency virus-1, hepatitis delta virus and hepatitis B virus infections in 260 chronic carriers of hepatitis B virus. Hepatology. 1992;15:578-583.
5. Rockstroh JK, Spengler U, Sudhop T, et al. Immunosuppression may lead to progression of hepatitis C virus-associated liver disease in hemophiliacs coinfected with HIV. Am J Gastroenterol. 1996;91:2563-2568.
6. Bica I, McGovern B, Dhar R, et al. Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection. Clin Infect Dis. 2001;32:492-497.
7. Martin-Carbonero L, Soriano V, Valencia E, et al. Increasing impact of chronic viral hepatitis on hospital admissions and mortality among HIV-infected patients. AIDS Res Hum Retroviruses. 2001;17:1467-1471.
8. Soto B, Sanchez-Quijano A, Rodrigo L, et al. Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis [comment]. J Hepatol. 1997;26:1-5.
9. Cameron DW, Japour AJ, Xu Y, et al. Ritonavir and saquinavir combination therapy for the treatment of HIV infection. AIDS. 1999;13:213-224.
10. Gonzalez-Requena D, Nunez M, Jimenez-Nacher I, et al. liver toxicity of lopinavir-containing regimens in HIV-infected patients with or without hepatitis C coinfection [short communication]. AIDS Res Hum Retroviruses. 2004;20:698-700.
11. Sulkowski MS, Thomas DL, Chaisson RE, et al. Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. JAMA. 2000;283:74-80.
12. Ungo J, Jones D, Ashkin D, et al. Antituberculosis drug-induced hepatotoxicity. The role of hepatitis C virus and the human immunodeficiency virus. Am J Respir Crit Care Med. 1998;157:1871-1876.
13. Wilkinson GR. Drug metabolism and variability among patients in drug response. New Engl J Med. 2005;352:2211-2221.
14. Zapor MJ, Cozza KL, Wynn GH, et al. Antiretrovirals, part II: focus on non-protease inhibitor antiretrovirals (NRTIs, NNRTIs, and fusion inhibitors). Psychosomatics. 2004;45:524-535.
15. Greenblatt DJ, von Moltke LL, Harmatz JS, et al. Alprazolam-ritonavir interaction: implications for product labeling. Clin Pharmacol Ther. 2000;67:335-341.
16. Hsu A, Granneman GR, Bertz RJ. Ritonavir. Clinical pharmacokinetics and interactions with other anti-HIV agents. Clin Pharmacokinet. 1998;35:275-291.
17. Benson CA, Deeks SG, Brun SC, et al. Safety and antiviral activity at 48 weeks of lopinavir/ritonavir plus nevirapine and 2 nucleoside reverse-transcriptase inhibitors in human immunodeficiency virus type 1-infected protease inhibitor-experienced patients. J Infect Dis. 2002;185:599-607.
18. Kempf DJ, Marsh KC, Kumar G, et al. Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir. Antimicrob Agents Chemother. 1997;41:654-660.
19. Trouvin JH, Farinotti R, Haberer JP, et al. Pharmacokinetics of midazolam in anaesthetized cirrhotic patients. Br J Anaesth. 1988;60:762-767.
20. Pentikainen PJ, Valisalmi L, Himberg JJ, et al. Pharmacokinetics of midazolam following intravenous and oral administration in patients with chronic liver disease and in healthy subjects. J Clin Pharmacol. 1989;29:272-277.
21. Chalasani N, Gorski JC, Patel NH, et al. Hepatic and intestinal cytochrome P450 3A activity in cirrhosis: effects of transjugular intrahepatic portosystemic shunts. Hepatology. 2001;34:1103-1108.
22. Kroboth PD, Maxwell RA, Fleishaker JC, et al. Comparison of adinazolam pharmacokinetics and effects in healthy and cirrhotic subjects. J Clin Pharmacol. 1991;31:580-586.
23. von Moltke LL, Greenblatt DJ, Schmider J, et al. In vitro approaches to predicting drug interactions in vivo. Biochem Pharmacol. 1998;55:113-122.
24. Yang LQ, Li SJ, Cao YF, et al. Different alterations of cytochrome P450 3A4 isoform and its gene expression in livers of patients with chronic liver diseases. World J Gastroenterol. 2003;9:359-363.
25. George J, Murray M, Byth K, et al. Differential alterations of cytochrome P450 proteins in livers from patients with severe chronic liver disease. Hepatology. 1995;21:120-128.
26. Bauer LA, O'Sullivan T, Reiss WG, et al. Liver blood flow, antipyrine clearance, and antipyrine metabolite formation clearance in patients with chronic active hepatitis and alcoholic cirrhosis. Br J Clin Pharmacol. 1994;37:375-381.
27. Krausz Y, Zylber-Katz E, Levy M. Antipyrine clearance and its correlation to routine liver function tests in patients with liver disease. Int J Clin Pharmacol Ther Toxicol. 1980;18:253-257.
28. Abdallah H, Jerling M. Effect of hepatic impairment on the multiple-dose pharmacokinetics of ranolazine sustained-release tablets. J Clin Pharmacol. 2005;45:802-809.
29. Shiffman ML, Luketic VA, Sanyal AJ, et al. Hepatic lidocaine metabolism and liver histology in patients with chronic hepatitis and cirrhosis. Hepatology. 1994;19:933-940.
30. Becquemont L, Chazouilleres O, Serfaty L, et al. Effect of interferon alpha-ribavirin bitherapy on cytochrome P450 1A2 and 2D6 and N-acetyltransferase-2 activities in patients with chronic active hepatitis C. Clin Pharmacol Ther. 2002;71:488-495.
31. Grieco A, Castellano R, Matera A, et al. Antipyrine clearance in chronic and neoplastic liver diseases: a study of 518 patients. J Gastroenterol Hepatol. 1998;13:460-466.
32. Williams SJ, Farrell GC. Serial antipyrine clearance studies detect altered hepatic metabolic function during spontaneous and interferon-induced changes in chronic hepatitis B disease activity. Hepatology. 1989;10:192-197.
33. Coverdale SA, Samarasinghe DA, Lin R, et al. Changes in antipyrine clearance and platelet count, but not conventional liver tests, correlate with fibrotic change in chronic hepatitis C: value for predicting fibrotic progression. Am J Gastroenterol. 2003;98:1384-1390.
34. Shedlofsky SI, Israel BC, Tosheva R, et al. Endotoxin depresses hepatic cytochrome P450-mediated drug metabolism in women. Br J Clin Pharmacol. 1997;43:627-632.
35. van Ess PJ, Mattson MP, Blouin RA. Enhanced induction of cytochrome P450 enzymes and CAR binding in TNF (p55(-/-)/p75(-/-)) double receptor knockout mice following phenobarbital treatment. J Pharmacol Exp Ther. 2002;300:824-830.
36. Haas CE, Kaufman DC, Jones CE, et al. Cytochrome P450 3A4 activity after surgical stress. Crit Care Med. 2003;31:1338-1346.
37. Olubodun JO, Ochs HR, von Moltke LL, et al. Pharmacokinetic properties of zolpidem in elderly and young adults: possible modulation by testosterone in men. Br J Clin Pharmacol. 2003;56:297-304.
38. Zifroni A, Schiavi RC, Schaffner F. Sexual function and testosterone levels in men with nonalcoholic liver disease. Hepatology. 1991;14:479-482.
39. Grinspoon S, Corcoran C, Lee K, et al. Loss of lean body and muscle mass correlates with androgen levels in hypogonadal men with acquired immunodeficiency syndrome and wasting. J Clin Endocrinol Metabol. 1996;81:4051-4058.
40. Tsunoda SM, Velez RL, von Moltke LL, et al. Differentiation of intestinal and hepatic cytochrome P450 3A activity with use of midazolam as an in vivo probe: effect of ketoconazole. Clin Pharmacol Ther. 1999;66:461-471.
41. Gorski JC, Jones DR, Haehner-Daniels BD, et al. The contribution of intestinal and hepatic CYP3A to the interaction between midazolam and clarithromycin. Clin Pharmacol Ther. 1998;64:133-143.
42. Greenblatt DJ, Abernethy DR, Locniskar A, et al. Effect of age, gender, and obesity on midazolam kinetics. Anesthesiology. 1984;61:27-35.
43. Cotreau MM, von Moltke LL, Greenblatt DJ. The influence of age and sex on the clearance of cytochrome P450 3A substrates. Clin Pharmacokinet. 2005;44:33-60.
44. Greenblatt DJ, von Moltke LL, Harmatz JS, et al. Time course of recovery of cytochrome p450 3A function after single doses of grapefruit juice. Clin Pharmacol Ther. 2003;74:121-129.
45. Bornemann LD, Min BH, Crews T, et al. Dose dependent pharmacokinetics of midazolam. Eur J Clin Pharmacol. 1985;29:91-95.
46. Farkas D, Oleson LE, Zhao Y, et al. Pomegranate juice does not impair clearance of oral or intravenous midazolam, a probe for cytochrome P450-3A activity: comparison with grapefruit juice. J Clin Pharmacol. 2007;47:286-294.
47. Arendt RM, Greenblatt DJ, Garland WA. Quantitation by gas chromatography of the 1- and 4-hydroxy metabolites of midazolam in human plasma. Pharmacology. 1984;29:158-164.
48. Granda BW, Giancarlo GM, von Moltke LL, et al. Analysis of ritonavir in plasma/serum and tissues by high-performance liquid chromatography. J Pharmacol Toxicol Methods. 1998;40:235-239.
49. Kawasaki S, Sugiyama Y, Iga T, et al. Hepatic clearances of antipyrine, indocyanine green, and galactose in normal subjects and in patients with chronic liver diseases. Clin Pharmacol Ther. 1988;44:217-224.
50. Zoli M, Magalotti D, Bianchi G, et al. Functional hepatic flow and Doppler-assessed total hepatic flow in control subjects and in patients with cirrhosis. J Hepatol. 1995;23:129-134.
51. Poynard T, Bedossa P. Age and platelet count: a simple index for predicting the presence of histological lesions in patients with antibodies to hepatitis C virus. METAVIR and CLINIVIR Cooperative Study Groups. J Viral Hepat. 1997;4:199-208.
52. Wai CT, Greenson JK, Fontana RJ, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518-526.
53. von Moltke LL, Greenblatt DJ, Schmider J, et al. Midazolam hydroxylation by human liver microsomes in vitro: inhibition by fluoxetine, norfluoxetine, and by azole antifungal agents. J Clin Pharmacol. 1996;36:783-791.
54. He P, Court MH, Greenblatt DJ, et al. Genotype-phenotype associations of cytochrome P450 3A4 and 3A5 polymorphism with midazolam clearance in vivo. Clin Pharmacol Ther. 2005;77:373-387.
55. Wandel C, Witte JS, Hall JM, et al. CYP3A activity in African American and European American men: population differences and functional effect of the CYP3A4*1B5′-promoter region polymorphism. Clin Pharmacol Ther. 2000;68:82-91.
56. Tateishi T, Watanabe M, Nakura H, et al. CYP3A activity in European American and Japanese men using midazolam as an in vivo probe. Clin Pharmacol Ther. 2001;69:333-339.
57. Tucker AN, Tkaczuk KA, Lewis LM, et al. Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005;217:61-72.
58. Greenblatt DJ, Harmatz JS, von Moltke LL, et al. Age and gender effects on the pharmacokinetics and pharmacodynamics of triazolam, a cytochrome P450 3A substrate. Clin Pharmacol Ther. 2004;76:467-479.
59. Bannister P, Oakes J, Sheridan P, et al. Sex hormone changes in chronic liver disease: a matched study of alcoholic versus non-alcoholic liver disease. Q J Med. 1987;63:305-313.
60. Lamba JK, Lin YS, Schuetz EG, et al. Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev. 2002;54:1271-1294.
61. Lamba JK, Lin YS, Thummel K, et al. Common allelic variants of cytochrome P4503A4 and their prevalence in different populations. Pharmacogenetics. 2002;12:121-132.
62. Eap CB, Buclin T, Cucchia G, et al. Oral administration of a low dose of midazolam (75 μg) as an in vivo probe for CYP3A activity. Eur J Clin Pharmacol. 2004;60:237-246.
63. Wyen C, Fuhr U, Frank D, et al. Effect of an antiretroviral regimen containing ritonavir boosted lopinavir on intestinal and hepatic CYP3A, CYP2D6 and P-glycoprotein in HIV-infected patients. Clin Pharmacol Ther. 2008;84:75-82.
64. von Moltke LL, Greenblatt DJ, Grassi JM, et al. Protease inhibitors as inhibitors of human cytochromes P450: high risk associated with ritonavir. J Clin Pharmacol. 1998;38:106-111.
65. Perloff ES, Duan SX, Skolnik PR, et al. Atazanavir: effects on P-glycoprotein transport and CYP3A metabolism in vitro. Drug Metab Dispos. 2005;33:764-770.
66. Weemhoff JL, von Moltke LL, Richert C, et al. Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir. J Pharm Pharmacol. 2003;55:381-386.
67. von Moltke LL, Greenblatt DJ, Granda BW, et al. Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse transcriptase inhibitors. J Clin Pharmacol. 2001;41:85-91.
68. Dixit V, Hariparsad N, Li F, et al. Cytochrome P450 enzymes and transporters induced by anti-human immunodeficiency virus protease inhibitors in human hepatocytes: implications for predicting clinical drug interactions. Drug Metab Dispos. 2007;35:1853-1859.
69. Culm-Merdek KE, von Moltke LL, Gan L, et al. Effect of extended exposure to grapefruit juice on cytochrome P450 3A activity in humans: comparison with ritonavir. Clin Pharmacol Ther. 2006;79:243-254.
70. Perloff MD, von Moltke LL, Greenblatt DJ. Ritonavir and dexamethasone induce expression of CYP3A and P-glycoprotein in rats. Xenobiotica. 2004;34:133-150.
71. von Moltke LL, Durol AL, Duan SX, et al. Potent mechanism-based inhibition of human CYP3A in vitro by amprenavir and ritonavir: comparison with ketoconazole. Eur J Clin Pharmacol. 2000;56:259-261.
72. Fellay J, Marzolini C, Decosterd L, et al. Variations of CYP3A activity induced by antiretroviral treatment in HIV-1 infected patients. Eur J Clin Pharmacol. 2005;60:865-873.
73. Mouly S, Rizzo-Padoin N, Simoneau G, et al. Effect of widely used combinations of antiretroviral therapy on liver CYP3A4 activity in HIV-infected patients. Br J Clin Pharmacol. 2006;62:200-209.
74. Andersen V, Pedersen N, Larsen NE, et al. Intestinal first pass metabolism of midazolam in liver cirrhosis - effect of grapefruit juice. Br J Clin Pharmacol. 2002;54:120-124.
75. Lim ML, Min SS, Eron JJ, et al. Coadministration of lopinavir/ritonavir and phenytoin results in two-way drug interaction through cytochrome P-450 induction. JAIDS. 2004;36:1034-1040.
76. Mouly S, Lown KS, Kornhauser D, et al. Hepatic but not intestinal CYP3A4 displays dose-dependent induction by efavirenz in humans. Clin Pharmacol Ther. 2002;72:1-9.
77. Lown KS, Mayo RR, Leichtman AB, et al. Role of intestinal P-glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclosporine. Clin Pharmacol Ther. 1997;62:248-260.
78. Gutmann H, Fricker G, Drewe J, et al. Interactions of HIV protease inhibitors with ATP-dependent drug export proteins. Mol Pharmacol. 1999;56:383-389.
79. Perloff MD, von Moltke LL, Marchand JE, et al. Ritonavir induces P-glycoprotein expression, multidrug resistance-associated protein (MRP1) expression, and drug transporter-mediated activity in a human intestinal cell line. J Pharm Sci. 2001;90:1829-1837.
80. Knox TA, Spiegelman D, Skinner SC, et al. Diarrhea and abnormalities of gastrointestinal function in a cohort of men and women with HIV infection. Am J Gastroenterol. 2000;95:3482-3489.
81. Mouly SJ, Matheny C, Paine MF, et al. Variation in oral clearance of saquinavir is predicted by CYP3A5*1 genotype but not by enterocyte content of cytochrome P450 3A5. Clin Pharmacol Ther. 2005;78:605-618.
82. Slain D, Pakyz A, Israel DS, et al. Variability in activity of hepatic CYP3A4 in patients infected with HIV. Pharmacotherapy. 2000;20:898-907.
83. Yeh RF, Gaver VE, Patterson KB, et al. Lopinavir/ritonavir induces the hepatic activity of cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP1A2 but inhibits the hepatic and intestinal activity of CYP3A as measured by a phenotyping drug cocktail in healthy volunteers. JAIDS. 2006;42:52-60.
84. Peng J, Pulido F, Kemmis Causemaker S, et al. Pharmacokinetics of lopinavir/ritonavir in HIV/hepatitis C virus-coinfected subjects with hepatic impairment. J Clin Pharmacol. 2006;46:265-274.
85. Molto J, Valle M, Blanco A, et al. Lopinavir/ritonavir pharmacokinetics in HIV and hepatitis C virus co-infected patients without liver function impairment: influence of liver fibrosis. Clin Pharmacokinet. 2007;46:85-92.