title: Non-nucleoside reverse transcriptase inhibitors: a review on pharmacokinetics, pharmacodynamics, safety and tolerability.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV) type-1 non-nucleoside and nucleoside reverse transcriptase inhibitors (NNRTIs) are key drugs of highly active antiretroviral therapy (HAART) in the clinical management of acquired immune deficiency syndrome (AIDS)/HIV infection.
  
  
  CONCLUSIONS
  First-generation NNRTIs, nevirapine (NVP), delavirdine (DLV) and efavirenz (EFV) are drugs with a low genetic barrier and poor resistance profile, which has led to the development of new generations of NNRTIs. Second-generation NNRTIs, etravirine (ETR) and rilpivirine (RPV) have been approved by the Food and Drug Administration and European Union, and the next generation of drugs is currently being clinically developed. This review describes recent clinical data, pharmacokinetics, metabolism, pharmacodynamics, safety and tolerability of commercialized NNRTIs, including the effects of sex, race and age differences on pharmacokinetics and safety. Moreover, it summarizes the characteristics of next-generation NNRTIs: lersivirine, GSK 2248761, RDEA806, BILR 355 BS, calanolide A, MK-4965, MK-1439 and MK-6186.
  
  
  CONCLUSIONS
  This review presents a wide description of NNRTIs, providing useful information for researchers interested in this field, both in clinical use and in research.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Burjassot, Valencia, Spain.
authors.forename: Iris
authors.initials: I
authors.lastname: Usach
authors.forename: Virginia
authors.initials: V
authors.lastname: Melis
authors.forename: José-Esteban
authors.initials: JE
authors.lastname: Peris
mesh_terms: D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D017277:Drug Approval; D055808:Drug Discovery / Q000639:trends; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D016896:Treatment Outcome
chemical_list: D054303:HIV Reverse Transcriptase
keywords: delavirdine; efavirenz; etravirine; human immunodeficiency virus; nevirapine; next-generation non-nucleoside reverse transcriptase inhibitors; non-nucleoside reverse transcriptase inhibitors; rilpivirine