Evaluation of steady-state pharmacokinetic interactions between ritonavir-boosted BILR 355, a non-nucleoside reverse transcriptase inhibitor, and lamivudine/zidovudine in healthy subjects

Journal of Clinical Pharmacy and Therapeutics

Volumn 37, Issue 1, 2012, Pages 81-88

  Huang, F ^a   Allen, L ^a   Huang, D B ^a   Moy, F ^a   Vinisko, R ^a   Nguyen, T ^a   Rowland, L ^a   MacGregor, T R ^a   Castles, M A ^a   Robinson, P ^a  

^a BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

BILR 355; drug drug interaction; lamivudine; non nucleoside reverse transcriptase inhibitor; organic cation transporter; zidovudine

Indexed keywords

BILR 355; EMTRICITABINE; LAMIVUDINE PLUS ZIDOVUDINE; LOPINAVIR PLUS RITONAVIR; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; RITONAVIR; TIPRANAVIR; UNCLASSIFIED DRUG;

ADULT; ARTICLE; BLOOD SAMPLING; CONTROLLED STUDY; DIARRHEA; DIZZINESS; DRUG BLOOD LEVEL; DRUG ELIMINATION; DRUG EXPOSURE; DRUG HALF LIFE; DRUG INHIBITION; DRUG SAFETY; DRUG URINE LEVEL; FATIGUE; FEMALE; HEADACHE; HUMAN; HUMAN EXPERIMENT; MALE; MYALGIA; NAUSEA; NORMAL HUMAN; OPEN STUDY; PHASE 1 CLINICAL TRIAL; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL; SOMNOLENCE; STEADY STATE; UPPER ABDOMINAL PAIN; VOMITING;

ADULT; ANTI-HIV AGENTS; AREA UNDER CURVE; AZEPINES; DRUG COMBINATIONS; DRUG INTERACTIONS; FEMALE; HALF-LIFE; HIV PROTEASE INHIBITORS; HUMANS; LAMIVUDINE; MALE; MIDDLE AGED; PROSPECTIVE STUDIES; PYRIDINES; REVERSE TRANSCRIPTASE INHIBITORS; RITONAVIR; YOUNG ADULT; ZIDOVUDINE;

EID: 84856352143     PISSN: 02694727     EISSN: 13652710     Source Type: Journal    
DOI: 10.1111/j.1365-2710.2010.01235.x     Document Type: Article

References (35)

1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. December 1, 2009; 1-161. Available at. Accessed (November 3, 2010)
2. Boone LR,. Next-generation HIV-1 non-nucleoside reverse transcriptase inhibitors. Current Opinion in Investigional Drugs, 2006; 7: 128-135. (Pubitemid 43230908)
3. Deeks SG,. International perspectives on antiretroviral resistance. Nonnucleoside reverse transcriptase inhibitor resistance. Journal of Acquired Immune Deficiency Syndromes, 2001; 26 (Suppl. 1): S25-S33.
4. De Clercq E,. What can be expected from non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the treatment of human immunodeficiency virus type 1 (HIV-1) infections? Reviews in Medical Virology, 1996; 6: 97-117.
5. De Clercq E,. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) for the treatment of human immunodeficiency virus type 1 (HIV-1) infections: strategies to overcome drug resistance development. Medicinal Research Reviews, 1996; 16: 125-157. (Pubitemid 26099986)
6. De Clercq E,. Non-nucleoside reverse transcriptase inhibitors (NNRTIs): past, present, and future. Chemistry & Biodiversity, 2004; 1: 44-64.
7. Bonneau P, Robinson PA, Duan J, et al. (2005) Antiviral characterization and human experience with BILR 355 BS, a novel next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with a broad antiHIV-1 profile. Boston: 12th Conference on Retroviruses and Opportunistic Infections. Feb 22-25, 2005. [Abstract # 558].
8. Huang F, Koenen-Bergmann M, MacGregor TR, et al. Pharmacokinetic and safety evaluation of BILR 355, a second generation non-nucleoside reverse transcriptase inhibitor, in healthy volunteers. Antimicrobial Agents and Chemotherapy, 2008; 52: 4300-4307.
9. Huang F, Drda K, MacGregor TR, et al. Pharmacokinetics of BILR 355 after multiple oral dosing co-administered with low dose of ritonavir. Antimicrobial Agents and Chemotherapy, 2009; 53: 95-103.
10. Cammack N, Rouse P, Marr CL, et al. Cellular metabolism of (-) enantiomeric 2'-deoxy-3'-thiacytidine. Biochemical Pharmacology, 1992; 43: 2059-2064.
11. Coates JA, Cammack N, Jenkinson HJ, et al. (-)-2'-deoxy-3'-thiacytidine is a potent, highly selective inhibitor of human immunodeficiency virus type 1 and type 2 replication in vitro. Antimicrobial Agents and Chemotherapy, 1992; 36: 733-739.
12. Wilde MI, Langtry HD,. Zidovudine. An update of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs, 1993; 46: 515-578. (Pubitemid 23292122)
13. Bhana N, Ormrod D, Perry CM, et al. Zidovudine: a review of its use in the management of vertically-acquired pediatric HIV infection. Paediatric Drugs, 2002; 4: 515-553. (Pubitemid 34876157)
14. Tisdale M, Kemp SD, Parry NR, et al. Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3'-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase. Proceedings of the National Academy of Sciences of the United States of America, 1993; 90: 5653-5656. (Pubitemid 23176219)
15. Katlama C, Ingrand D, Loveday C, et al. Safety and efficacy of lamivudine-zidovudine combination therapy in antiretroviral-naive patients. A randomized controlled comparison with zidovudine monotherapy. Lamivudine European HIV Working Group. JAMA, 1996; 276: 118-125.
16. Staszewski S, Loveday C, Picazo JJ, et al. Safety and efficacy of lamivudine-zidovudine combination therapy in zidovudine-experienced patients. A randomized controlled comparison with zidovudine monotherapy. Lamivudine European HIV Working Group. JAMA, 1996; 276: 111-117.
17. Bartlett JA, Benoit SL, Johnson VA, et al. Lamivudine plus zidovudine compared with zalcitabine plus zidovudine in patients with HIV infection. A randomized, double-blind, placebo-controlled trial. North American HIV Working Party. Annals of Internal Medicine, 1996; 125: 161-172. (Pubitemid 126449258)
18. Huang F, Scholl P, Huang DB, et al. (2010) Co-administration with lopinavir and ritonavir (LPV/r) decreases the exposure to BILR 355, a non-nucleoside reverse transcriptase inhibitor (NNRTI), in healthy volunteers. Journal of Clinical Pharmacology, published online doi: doi
19. Huang F, Scholl P, Huang DB, et al. (2010) Concomitant administration of BILR 355/r with emtricitabine/tenofovir disoproxil fumarate increases exposure to emtricitabine and tenofovir: a randomized, open-Label, prospective study. Basic & Clinical Pharmacology & Toxicology, published online doi:.
20. GlaxoSmithKline. (2009) COMBIVIR prescribing information. Research Triangle Park, NC 27709: GlaxoSmithKline.
21. Johnson MA, Moore KH, Yuen GJ, et al. Clinical pharmacokinetics of lamivudine. Clinical Pharmacokinetics, 1999; 36: 41-66. (Pubitemid 29056000)
22. Jung N, Lehmann C, Rubbert A, et al. Relevance of the organic cation transporters 1 and 2 for antiretroviral drug therapy in human immunodeficiency virus infection. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 2008; 36: 1616-1623.
23. Minuesa G, Volk C, Molina-Arcas M, et al. Transport of lamivudine [(-)-beta-L-2',3'-dideoxy-3'-thiacytidine] and high-affinity interaction of nucleoside reverse transcriptase inhibitors with human organic cation transporters 1, 2, and 3. The Journal of Pharmacology and Experimental Therapeutics, 2009; 329: 252-261.
24. Nakatani-Freshwater T, Babayeva M, Dontabhaktuni A, et al. Effects of trimethoprim on the clearance of apricitabine, a deoxycytidine analog reverse transcriptase inhibitor, and lamivudine in the isolated perfused rat kidney. The Journal of Pharmacology and Experimental Therapeutics, 2006; 319: 941-947.
25. Takubo T, Kato T, Kinami J, et al. Effect of trimethoprim on the renal clearance of lamivudine in rats. The Journal of Pharmacy and Pharmacology, 2000; 52: 315-320. (Pubitemid 30189387)
26. Sweeney KR, Hsyu PH, Statkevich P, et al. Renal disposition and drug interaction screening of (-)-2'-deoxy-3'-thiacytidine (3TC) in the isolated perfused rat kidney. Pharmaceutical Research, 1995; 12: 1958-1963. (Pubitemid 26031783)
27. Moore KH, Yuen GJ, Raasch RH, et al. Pharmacokinetics of lamivudine administered alone and with trimethoprim-sulfamethoxazole. Clinical Pharmacology and Therapeutics, 1996; 59: 550-558.
28. Nakatani-Freshwater T, Taft DR,. Renal excretion of emtricitabine II. Effect of trimethoprim on emtricitabine excretion: in vitro and in vivo studies. Journal of Pharmaceutical Sciences, 2008; 97: 5411-5420.
29. Nakatani-Freshwater T, Taft DR,. Renal excretion of emtricitabine I: effects of organic anion, organic cation, and nucleoside transport inhibitors on emtricitabine excretion. Journal of Pharmaceutical Sciences, 2008; 97: 5401-5410.
30. Huang F, MacGregor TR, Yong CL, et al. (2009) Mixed effects pharmacokinetic modeling of BILR 355 and its major metabolite BILR 516. 2009 American Association of Pharmaceutical Scientists Annual Meeting. Nov 8-12, 2008; Los Angels, CA.
31. Li Y, Lai G, Xu J, et al. (2009) Metabolic switching of BILR 355 in the presence of ritonavir II: elucidation of metabolic pathway for the formation of BILR 516. The 16th North American Regional ISSX Meeting, Baltimore, Maryland, October 18-22, 2009, poster #201. Drug Metabolism Reviews, 41 (Suppl. 3).
32. Wang X, Furukawa T, Nitanda T, et al. Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Molecular Pharmacology, 2003; 63: 65-72. (Pubitemid 36043809)
33. Wang X, Nitanda T, Shi M, et al. Induction of cellular resistance to nucleoside reverse transcriptase inhibitors by the wild-type breast cancer resistance protein. Biochemical Pharmacology, 2004; 68: 1363-1370. (Pubitemid 39179395)
34. Kim HS, Sunwoo YE, Ryu JY, et al. The effect of ABCG2 V12M, Q141K and Q126X, known functional variants in vitro, on the disposition of lamivudine. British Journal of Clinical Pharmacology, 2007; 64: 645-654. (Pubitemid 47568815)
35. Fletcher CV, Kawle SP, Kakuda TN, et al. Zidovudine triphosphate and lamivudine triphosphate concentration-response relationships in HIV-infected persons. AIDS, 2000; 14: 2137-2144.