Pharmacokinetic Enhancers in HIV Therapeutics

Maximal and durable viral load suppression is one of the most important goals of HIV therapy and is directly related to adequate drug exposure. Protease inhibitors (PIs), an important component of the antiretroviral armada, were historically associated with poor oral bioavailability and high pill bu...

Full description

Saved in:

Bibliographic Details
Published in:	Clinical pharmacokinetics Vol. 53; no. 10; pp. 865 - 872
Main Authors:	Larson, Kajal B., Wang, Kun, Delille, Cecile, Otofokun, Igho, Acosta, Edward P.
Format:	Journal Article
Language:	English
Published:	Cham Springer International Publishing 01-10-2014 Adis International Springer Nature B.V
Subjects:	Anti-HIV Agents - metabolism Anti-HIV Agents - pharmacokinetics Anti-HIV Agents - pharmacology Biological and medical sciences Carbamates - administration & dosage Carbamates - pharmacology Cobicistat Cytochrome P-450 CYP3A Inhibitors - administration & dosage Cytochrome P-450 CYP3A Inhibitors - pharmacology Drug Combinations Drug Interactions Drug Therapy, Combination General pharmacology HIV Protease Inhibitors - metabolism HIV Protease Inhibitors - pharmacokinetics HIV Protease Inhibitors - pharmacology Human viral diseases Humans Immunodeficiencies Immunodeficiencies. Immunoglobulinopathies Immunopathology Infectious diseases Internal Medicine Leading Article Medical sciences Medicine Medicine & Public Health Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions Pharmacology. Drug treatments Pharmacology/Toxicology Pharmacotherapy Ritonavir - metabolism Ritonavir - pharmacokinetics Ritonavir - pharmacology Thiazoles - administration & dosage Thiazoles - pharmacology Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Tenofovir Saquinavir Atazanavir Ritonavir Tenofovir Disoproxil Fumarate Infection Virus Human Immunopathology Treatment Viral disease Retroviridae AIDS Human immunodeficiency virus Pharmacokinetics Immune deficiency Lentivirus
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Maximal and durable viral load suppression is one of the most important goals of HIV therapy and is directly related to adequate drug exposure. Protease inhibitors (PIs), an important component of the antiretroviral armada, were historically associated with poor oral bioavailability and high pill burden. However, because the PIs are metabolized by cytochrome P450 (CYP) 3A enzymes, intentional inhibition of these enzymes leads to higher drug exposure, lower pill burden, and therefore simplified dosing schedules with this class of drug. This is the basis of pharmacokinetic enhancement. In HIV therapy, two pharmacokinetic enhancers or boosting agents are used: ritonavir and cobicistat. Both agents inhibit CYP3A4, with cobicistat being a more specific CYP inhibitor than ritonavir. Unlike ritonavir, cobicistat does not have antiretroviral activity. Cobicistat has been evaluated in clinical trials and was recently approved in the USA as a fixed-dose combination with the integrase inhibitor, elvitegravir and two nucleos(t)ide analogs. Additional studies are examining cobicistat in fixed-dose combinations with various PIs. In this review, we summarize current knowledge of these agents and clinically relevant drug regimens and ongoing trials. Studies with elvitegravir and the novel PI TMC319011 are also discussed.
ISSN:	0312-5963 1179-1926
DOI:	10.1007/s40262-014-0167-9