Bioequivalence of a darunavir/cobicistat fixed-dose combination tablet versus single agents and food effect in healthy volunteers

Antiviral Therapy

Volumn 19, Issue 6, 2014, Pages 597-606

  Kakuda, Thomas N ^a   De Casteele, Tom Van ^b   Petrovic, Romana ^b   Neujens, Mark ^c   Salih, Hiba ^c   Opsomer, Magda ^b   Hoetelmans, Richard M W ^b  

^a JANSSEN RESEARCH AND DEVELOPMENT   (United States)

^b JANSSEN RESEARCH FOUNDATION   (Belgium)

^c CPU Janssen Pharmaceutica NV   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

COBICISTAT; COBICISTAT PLUS DARUNAVIR; DARUNAVIR; LOW DENSITY LIPOPROTEIN CHOLESTEROL; CARBAMIC ACID DERIVATIVE; DRUG COMBINATION; SULFONAMIDE; THIAZOLE DERIVATIVE;

ABNORMAL LABORATORY RESULT; ADULT; AREA UNDER THE CURVE; ARTICLE; BIOEQUIVALENCE; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIET RESTRICTION; DRUG SAFETY; DRUG TOLERABILITY; ELIMINATION HALF-LIFE; FEMALE; FOOD; FOOD DRUG INTERACTION; HEADACHE; HUMAN; HUMAN EXPERIMENT; LIPID DIET; MALE; MAXIMUM PLASMA CONCENTRATION; MUSCLE SPASM; NAUSEA; NORMAL HUMAN; OPEN STUDY; PHASE 1 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; ADOLESCENT; ADVERSE EFFECTS; CLINICAL TRIAL; DRUG COMBINATION; DRUG MONITORING; MIDDLE AGED; ORAL DRUG ADMINISTRATION; THERAPEUTIC EQUIVALENCE; YOUNG ADULT;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; CARBAMATES; DRUG COMBINATIONS; DRUG MONITORING; FEMALE; FOOD; HEALTHY VOLUNTEERS; HUMANS; MALE; MIDDLE AGED; SULFONAMIDES; THERAPEUTIC EQUIVALENCY; THIAZOLES; YOUNG ADULT;

EID: 84920163703     PISSN: 13596535     EISSN: 20402058     Source Type: Journal    
DOI: 10.3851/IMP2814     Document Type: Article

References (35)

1. DHHS guidelines: 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. 1-239 (Updated May 2014. Accessed 22 September 2014.) Available from http://aidsinfo.nih.gov/contentfiles/ lvguidelines/adultandadolescentgl.pdf
2. EACS. European AIDS Clinical Society Guidelines. (Updated June 2014. Accesssed 22 September 2014.) Available from http://www.eacsociety.org/ Portals/0/140601-EACS%20EN7.02.pdf
3. Thompson MA, Aberg JA, Hoy JF, et al. Antiretroviral treatment of adult HIV infection, 2012 recommendations of the International Antiviral Society-USA Panel. JAMA 2012; 308:387-402.
4. Williams I, Churchill D, Anderson J, et al. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012. HIV Med 2012; 13 Suppl 2:1-85.
5. Hull MW, Montaner JS. Ritonavir-boosted protease inhibitors in HIV therapy. Ann Med 2011; 43:375-388.
6. Vermeir M, Lachau-Durand S, Mannens G, et al. Absorption, metabolism, and excretion of darunavir, a new protease inhibitor, administered alone and with low-dose ritonavir in healthy subjects. Drug Metab Dispos 2009; 37:809-820.
7. Samaras K, Richardson R, Carr A. Postprandial lipid effects of low-dose ritonavir vs. raltegravir in HIV-uninfected patients. AIDS 2010; 24:1727-1731.
8. Foisy MM, Yakiwchuk EM, Hughes CA. Induction effects of ritonavir: implications for drug interactions. Ann Pharmacother 2008; 42:1048-1059.
9. Xu L, Liu H, Murray B, et al. Cobicistat (GS-9350): a potent and selective inhibitor of human CYP 3A as a novel pharmacoenhancer. ACS Med Chem Lett 2010; 1:209-213.
10. Mathias AA, German P, Murray BP, et al. Pharmacokinetics and pharmacodynamics of GS-9350: a novel pharmacokinetic enhancer without anti-HIV activity. Clin Pharmacol Ther 2010; 87:322-329.
11. Lepist EI, Phan TK, Roy A, et al. Cobicistat boosts the intestinal absorption of transport substrates, including HIV protease inhibitors and GS-7340, in vitro. Antimicrob Agents Chemother 2012; 56:5409-5413.
12. Shah BM, Schafer JJ, Priano J, Squires KE. Cobicistat: a new boost for the treatment of human immunodeficiency virus infection. Pharmacotherapy 2013; 33:1107-1116.
13. Lepist El, Zhang X, Hao J, et al . Contribution of the organic anion transporter OAT2 to the renal active tubular secretion of creatinine and mechanism for serum creatinine elevations caused by cobicistat. Kidney Int 2014; 86:350-357.
14. Buscher A, Harman C, Kallen MA, Giordano TP. Impact of antiretroviral dosing frequency and pill burden on adherence among newly diagnosed, antiretroviral-naive HIV patients. Int J STD AIDS 2012; 23:351-355.
15. Juday T, Gupta S, Grimm K, Wagner S, Kim E. Factors associated with complete adherence to HIV combination antiretroviral therapy. HIV Clin Trials 2011; 12:71-78.
16. Sterrantino G, Santoro L, Bartolozzi D, Trotta M, Zaccarelli M. Self-reported adherence supports patient preference for the single tablet regimen (STR) in the current cART era. Patient Prefer Adherence 2012; 6:427-433.
17. Kauf TL, Davis KL, Earnshaw SR, Davis EA. Spillover adherence effects of fixed-dose combination HIV therapy. Patient Prefer Adherence 2012; 6:155-164.
18. Bangalore S, Kamalakkannan G, Parkar S, Messerli FH. Fixed dose combinations improve medication compliance: a meta-analysis. Am J Med 2007; 120:713-719.
19. German P, Warren D, West S, Hui J, Kearney BP. Pharmacokinetics and bioavailability of an integrase and novel pharmacoenhancer-containing single-tablet fixed-dose combination regimen for the treatment of HIV. J Acquir Immune Defic Syndr 2010; 55:323-329.
20. Ramanathan S, Warren D, Wei L, Kearney BP. Pharmacokinetic boosting of atazanavir with the pharmacoenhancer GS-9350 versus ritonavir. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy. 12-15 September 2009, San Francisco, CA, USA. Abstract A1-1301.
21. Elion R, Cohen C, Gathe J, et al. Phase 2 study of cobicistat versus ritonavir each with once-daily atazanavir and fixeddose emtricitabine/tenofovir DF in the initial treatment of HIV infection. AIDS 2011; 25:1881-1886.
22. Gallant JE, Koenig E, Andrade-Villanueva J, et al. Cobicistat versus ritonavir as a pharmacoenhancer of atazanavir plus emtricitabine/tenofovir disoproxil fumarate in treatmentnaïve HIV type 1-infected patients: week 48 results. J Infect Dis 2013; 208:32-39.
23. Mathias A, Liu HC, Warren D, Sekar V, Kearney BP. Relative bioavailability and pharmacokinetics of darunavir when boosted with the pharmacoenhancer GS-9350 versus RTV. 11th International Workshop on Clinical Pharmacology of HIV Therapy. 7-9 April 2010, Sorrento, Italy. Abstract 28.
24. Kakuda TN, Opsomer M, Timmers M, et al. Pharmacokinetics of darunavir in fixed-dose combination with cobicistat compared with coadministration of darunavir and ritonavir as single agents in healthy volunteers. J Clin Pharmacol 2014; 54:949-957.
25. Kakuda TN, Leopold L, Timmers M, et al. Bioavailability and bioequivalence of a darunavir 800-mg tablet formulation compared with the 400-mg tablet formulation. Int J Clin Pharmacol Ther 2014; 52:805-816.
26. Schöller-Gyüre M, Kakuda RN, Sekar V, et al. Pharmacokinetics of darunavir/ritonavir and TMC125 alone and coadministered in HIV-negative volunteers. Antivir Ther 2007; 12:789-796.
27. DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. Version 1.0. December 2004 (Updated August 2009. Accessed 19 June 2013.) Available from http://rsc.tech-res.com/Document/ safetyandpharmacovigilance/Table-for-Grading-Severity- of-Adult-Pediatric-Adverse-Events.pdf
28. Boffito M, Miralles D, Hill A. Pharmacokinetics, efficacy, and safety of darunavir/ritonavir 800/100 mg once-daily in treatment-naïve and -experienced patients. HIV Clin Trials 2008; 9:418-427.
29. Sekar V, Vanden Abeele C, Van Baelen B, et al. Pharmacokinetic-pharmacodynamic analyses of once-daily darunavir-ritonavir in the ARTEMIS study. 15th Conference on Retroviruses and Opportunistic Infections. 3-6 February 2008, Boston, MA, USA. Abstract 769.
30. Sekar V, De La Rosa G, Van de Casteele T, et al. Pharmacokinetic (PK) and pharmacodynamic analyses of once- and twice-daily darunavir/ritonavir (DRV/r) in the ODIN trial. 10th International Conference on Drug Therapy in HIV Infection. 7-11 November 2010, Glasgow, UK. Abstract P185.
31. Kakuda T, Brochot A, Tomaka F, et al. Generalized additive model analysis of the relationship between darunavir pharmacokinetics and pharmacodynamics following once-daily darunavir/ritonavir 800/100mg treatment in the Phase III trials ARTEMIS and ODIN. 11th International Congress on Drug Therapy in HIV Infection. 11-15 November 2012, Glasgow, UK. Abstract P072.
32. Connor J, Rafter N, Rodgers A. Do fixed-dose combination pills or unit-of-use packaging improve adherence? A systematic review. Bull World Health Organ 2004; 82: 935-939.
33. Sekar V, Kestens D, Spinosa-Guzman S, et al. The effect of different meal types on the pharmacokinetic of darunavir (TMC114)/ritonavir in HIV-negative healthy volunteers. J Clin Pharmacol 2007; 47:479-484.
34. Cahn P, Fourie J, Grinzstein B, et al . Week 48 analysis of once-daily vs. twice-daily darunavir/ritonavir in treatment-experienced HIV-1-infected patients. AIDS 2011; 25:929-939.
35. Orkin C, DeJesus E, Khanlou H, et al. Final 192-week efficacy and safety of once-daily darunavir/ritonavir compared with lopinavir/ritonavir in HIV-1-infected treatment-naive patients in the ARTEMIS trial. HIV Med 2013; 14:49-59.