Effects of CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers

British Journal of Clinical Pharmacology

Volumn 65, Issue SUPPL. 1, 2008, Pages 27-37

  Abel, Samantha ^a   Russell, Deborah ^a   Taylor Worth, Richard J ^a   Ridgway, Caroline E ^a   Muirhead, Gary J ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

CYP3A4; Drug interactions; Maraviroc; Pharmacokinetics; Protease inhibitors

Indexed keywords

ATAZANAVIR; CHEMOKINE RECEPTOR CCR5 ANTAGONIST; CYTOCHROME P450 3A4; CYTOCHROME P450 3A4 INHIBITOR; KETOCONAZOLE; LOPINAVIR; LOPINAVIR PLUS RITONAVIR; MARAVIROC; PLACEBO; PROTEINASE INHIBITOR; RITONAVIR; SAQUINAVIR; TIPRANAVIR; UNCLASSIFIED DRUG;

ABDOMINAL PAIN; ADULT; AREA UNDER THE CURVE; ARTICLE; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIARRHEA; DISEASE SEVERITY; DOSE RESPONSE; DRUG CROSS REACTIVITY; DRUG POTENCY; DRUG SAFETY; DRUG TOLERABILITY; ENZYME INHIBITION; FEMALE; FLATULENCE; HEADACHE; HUMAN; HUMAN EXPERIMENT; MALE; NAUSEA; NORMAL HUMAN; OPEN STUDY; PARALLEL DESIGN; PRIORITY JOURNAL; PROTEINASE INHIBITION; RANDOMIZED CONTROLLED TRIAL; STEADY STATE; VOLUNTEER;

EID: 40549127134     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2008.03133.x     Document Type: Article

References (29)

1. 1 Choo V. Combination superior to zidovudine in Delta trial. Lancet 1995 ; 346: 895.
2. 2 Collier AC, Coombs RW, Schoenfeld DA, Bassett RL, Timpone J, Baruch A, Jones M, Facey K, Whitacre C, McAuliffe VJ, Friedman HM, Merigan TC, Reichman RC, Hooper C, Corey L. Treatment of human immunodeficiency virus infection with saquinavir, zidovudine, and zalcitabine. AIDS Clinical Trials Group. N Engl J Med 1996 ; 334: 1011–7.
3. 3 Yeni PG, Hammer SM, Hirsch MS, Saag MS, Schechter M, Carpenter CC, Fishl MA, Gatell JM, Gazzard BG, Jacobsen DM, Katzenstein DA, Montaner JS, Richman DD, Schooley RT, Thompson MA, Vella S, Volberding PA. Treatment for adult HIV infection: 2004 recommendations of the International AIDS Society‐USA Panel. JAMA 2004 ; 292: 251–65.
4. 4 Rusconi S, Scozzafava A, Mastrolorenzo A, Supuran CT. New advances in HIV entry inhibitors development. Curr Drug Targets Infect Disord 2004 ; 4: 339–55.
5. 5 Tremblay C. Effects of HIV‐1 entry inhibitors in combination. Curr Pharm Des 2004 ; 10: 1861–5.
6. 6 Abel S, Van Der Ryst E, Rosario MC, Ridgway CE, Medhurst CG, Taylor‐Worth RJ, Muirhead GJ. Assessment of the pharmacokinetics, safety and tolerability of maraviroc, a novel CCR5 antagonist, in healthy volunteers. Br J Clin Pharmacol 2008 ; 65 (Suppl. 1): 5–18.
7. 7 Fatkenheuer G, Pozniak AL, Johnson MA, Plettenberg A, Staszewski S, Hoepelman AI, Saag MS, Goebel FD, Rockstroh JK, Dezube BJ, Jenkins TM, Medhurst C, Sullivan JF, Ridgway C, Abel S, James IT, Youle M, Van Der Ryst E. Efficacy of short‐term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV‐1. Nat Med 2005 ; 11: 1170–2.
8. 8 Lalezari J, Goodrich J, DeJesus E, Lampiris H, Gulick R, Saag M, Ridgway C, McHale M, Van Der Ryst E, Mayer H. Efficacy and safety of maraviroc (MVC) plus optimized background therapy (OBT) in viremic antiretroviral treatment experienced patients infected with CCR5‐tropic HIV‐1: 24‐week results of a phase 2b/3 study in the USA and Canada. In: 14th Conference on Retroviruses and Opportunistic Infections; 2007 February 25–28; Los Angeles, CA.
9. 9 Nelson M, Fätkenheuer G, Konourina I, Lazzarin A, Clumeck N, Horban A, Tawadrous M, Sullivan J, Mayer H, Van Der Ryst E. Efficacy and safety of maraviroc (MVC) plus optimized background therapy (OBT) in viremic, antiretroviral treatment experienced patients infected with CCR5‐tropic (R5) HIV‐1 in Europe, Australia and North America: 24‐week results. In: 14th Conference on Retroviruses and Opportunistic Infections; 2007 February 25–28; Los Angeles, CA.
10. 10 Walker DK, Abel S, Comby P, Muirhead GJ, Nedderman AN, Smith DA. Species differences in the disposition of the CCR5 antagonist, UK‐427,857, a new potential treatment for HIV. Drug Metab Dispos 2005 ; 33: 587–95.
11. 11 Hyland R, Jones B, Muirhead G. In vitro assessment of the CYP‐based drug–drug interaction potential of UK‐427,857. In: 5th International Workshop on Clinical Pharmacology of HIV Therapy; 2004 April 1–3; Rome, Italy.
12. 12 Ernest CS 2nd, Hall SD, Jones DR. Mechanism‐based inactivation of CYP3A by HIV protease inhibitors. J Pharmacol Exp Ther 2005 ; 312: 583–91.
13. 13 Lin JH, Yamazaki M. Role of P‐glycoprotein in pharmacokinetics: clinical implications. Clin Pharmacokinet 2003 ; 42: 59–98.
14. 14 Rathbun RC, Rossi DR. Low‐dose ritonavir for protease inhibitor pharmacokinetic enhancement. Ann Pharmacother 2002 ; 36: 702–6.
15. 15 Eagling VA, Back DJ, Barry MG. Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir. Br J Clin Pharmacol 1997 ; 44: 190–4.
16. 16 Flexner C. Dual protease inhibitor therapy in HIV‐infected patients: pharmacologic rationale and clinical benefits. Annu Rev Pharmacol Toxicol 2000 ; 40: 649–74.
17. 17 Moyle GJ, Back D. Principles and practice of HIV‐protease inhibitor pharmacoenhancement. HIV Med 2001 ; 2: 105–13.
18. 18 Van Heeswijk RP, Veldkamp A, Mulder JW, Meenhorst PL, Lange JM, Beijnen JH, Hoetelmans RM. Combination of protease inhibitors for the treatment of HIV‐1‐infected patients: a review of pharmacokinetics and clinical experience. Antivir Ther 2001 ; 6: 201–29.
19. 19 Hsu A, Granneman GR, Bertz RJ. Ritonavir. Clinical pharmacokinetics and interactions with other anti‐HIV agents. Clin Pharmacokinet 1998 ; 35: 275–91.
20. 20 Russell D, Bakhtyari A, Jazrawi RP, Whitlock L, Ridgway C, McHale M, Abel S. Multiple dose study to investigate the safety of UK‐427 857 (100 mg or 300 mg) BID for 28 days in healthy males and females. In: 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2003 September 14–17; Chicago, IL.
21. 21 Loose DS, Kan PB, Hirst MA, Marcus RA, Feldman D. Ketoconazole blocks adrenal steroidogenesis by inhibiting cytochrome P450‐dependent enzymes. J Clin Invest 1983 ; 71: 1495–9.
22. 22 Sheets JJ, Mason JI. Ketoconazole: a potent inhibitor of cytochrome P‐450‐dependent drug metabolism in rat liver. Drug Metab Dispos 1984 ; 12: 603–6.
23. 23 Abel S, Jenkins T, Whitlock LA, Ridgway CE, Muirhead GJ. Effects of CYP3A4 inducers with and without CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. Br J Clin Pharmacol 2008 ; 65 (Suppl. 1): 38–46.
24. 24 Poppe SM, Slade DE, Chong KT, Hinshaw RR, Pagano PJ, Markowitz M, Ho DD, Mo H, Gorman RR 3rd, Dueweke TJ, Thaisrivongs S, Tarpley WG. Antiviral activity of the dihydropyrone PNU‐140690, a new nonpeptidic human immunodeficiency virus protease inhibitor. Antimicrob Agents Chemother 1997 ; 41: 1058–63.
25. 25 Larder BA, Hertogs K, Bloor S, Van Den Eynde CH, DeCian W, Wang Y, Freimuth WW, Tarpley G. Tipranavir inhibits broadly protease inhibitor‐resistant HIV‐1 clinical samples. AIDS 2000 ; 14: 1943–8.
26. 26 MacGregor TR, Sabo JP, Norris SH, Johnson P, Galitz L, McCallister S. Pharmacokinetic characterization of different dose combinations of coadministered tipranavir and ritonavir in healthy volunteers. HIV Clin Trials 2004 ; 5: 371–82.
27. 27 Mukwaya G, MacGregor T, Hoelscher D, Heming T, Legg D, Kavanaugh K, Johnson P, Sabo JP, McCallister S. Interaction of ritonavir‐boosted tipranavir with loperamide does not result in loperamide‐associated neurologic side effects in healthy volunteers. Antimicrob Agents Chemother 2005 ; 49: 4903–10.
28. 28 Koudriakova T, Iatsimirskaia E, Utkin I, Gangl E, Vouros P, Storozhuk E, Orza D, Marinina J, Gerber N. Metabolism of the human immunodeficiency virus protease inhibitors indinavir and ritonavir by human intestinal microsomes and expressed cytochrome P4503A4/3A5: mechanism‐based inactivation of cytochrome P4503A by ritonavir. Drug Metab Dispos 1998 ; 26: 552–61.
29. 29 Olson DP, Scadden DT, D'Aquila RT, De Pasquale MP. The protease inhibitor ritonavir inhibits the functional activity of the multidrug resistance related‐protein 1 (MRP‐1). AIDS 2002 ; 16: 1743–7.