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Properties

Binding Affinity

PREZCOBIX® Contains Darunavir, Which Closely and Tightly Binds to HIV-1 Protease1

Binding Affinity visual

Adapted with permission from Ghosh AK et al. Angew Chem Int Ed. 2012;51:1778-1802.

1

  • Tightly binds to HIV-1 protease1
    • Fast association rate, slow dissociation rate1,2

2

  • Enhanced binding affinity is related to its ability to form an extensive network of hydrogen-bonding interactions within the HIV-1 protease active site2
  • Can sustain a substantial decrease in its binding constant without compromising its activity entirely3

3

  • Because of its molecular flexibility, darunavir can adapt itself to the changing shape of a mutant HIV protease4
  • Tight interactions with backbone atoms were consistently observed with mutant proteases5

References: 1. Diernyck I, De Wit M, Gustin E, et al. Binding kinetics of darunavir to human immunodeficiency virus type 1 protease explain the potent antiviral activity and high genetic barrier. J Virol. 2007;81:13845-13851. 2. Ghosh AK, Anderson DD, Weber IT, Mitsuya H. Enhancing protein backbone binding—a fruitful concept for combating drug-resistant HIV. Angew Chem Int Ed. 2012;1778-1802. 3. King NM, Prabu-Jeyabalan M, Nalivaika EA, et al. Structural and thermodynamic basis for the binding of TMC114, a next-generation human immunodeficiency virus type 1 protease inhibitor. J Virol. 2004;78:12012-12021. 4. Tremblay CL. Combating HIV resistance—focus on darunavir. Ther Clin Risk Manag. 2008;4:759-765. 5. Ghosh AK, Chapsal BD, Weber IT, Mitsuya H. Design of HIV protease inhibitors targeting protein backbone: an effective strategy for combating drug resistance. Accounts Chem Res. 2008;41:78-86.

Pharmacokinetics

PREZCOBIX® Provides Therapeutic Drug Levels at 24 Hours Post Dose1,2

PREZCOBIX® maintains plasma concentrations 37 times greater than EC50 at 24 hours*1,2

PK chart 01

The clinical implications of these data have not been established.

*Based on overall population PK sampling (n=298). 
A PK substudy was conducted in a subset of patients (n=60; 57 TN, 3 TE) enrolled in Safety Study 130. Intensive PK sampling was performed at a study visit occurring between Weeks 2 and 8.

EC50=half maximal effective concentration; OBR=optimized background regimen; PK=pharmacokinetic; SD=standard deviation; TE=treatment-experienced; TN=treatment-naïve.

References: 1. PREZCOBIX® [Prescribing Information]. Titusville, NJ: Janssen Therapeutics, Division of Janssen Products, LP. 2. Data on file. Janssen Therapeutics, Division of Janssen Products, LP.