[Pharmacokinetics, interactions and mechanism of action of maraviroc]

Enferm Infecc Microbiol Clin. 2008 Oct:26 Suppl 11:12-6. doi: 10.1016/s0213-005x(08)76558-3.
[Article in Spanish]

Abstract

Maraviroc (MVC, Celsentri) is an allosteric and reversible inhibitor of the CCR5 chemokine coreceptor. MVC is the first marketed CCR5 antagonist and the only oral entry inhibitor approved so far for the treatment of HIV infection. It has been approved for adults with previous antiretroviral exposure. MVC exclusively inhibits the replication of R5- tropic HIV-1 variants after binding to the transmembrane CCR5 receptor cavity. MVC is rapidly absorbed following oral administration, and plasma T(max) is achieved within 0.5- 4 hours after a 300 mg dose. Renal clearance is approximately 10-12 L/h. MVC is a substrate of the cytochrome P450 isoenzyme 3A4; therefore dose adjustments are required when co-administrated with other drugs that induce or inhibit CYP3A4. In addition, MVC dose adjustments are advised in patients with renal failure (CLcr <80 ml/min) only if they receive CYP3A4 inhibitors.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biological Availability
  • Biotransformation
  • CCR5 Receptor Antagonists*
  • Chemokines, CC / physiology
  • Clinical Trials as Topic / statistics & numerical data
  • Cyclohexanes / pharmacokinetics
  • Cyclohexanes / pharmacology*
  • Cytochrome P-450 CYP3A / metabolism
  • Cytochrome P-450 CYP3A Inhibitors
  • Drug Design
  • Drug Interactions
  • HIV Fusion Inhibitors / pharmacokinetics
  • HIV Fusion Inhibitors / pharmacology*
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism
  • HIV-1 / drug effects
  • HIV-1 / physiology*
  • Humans
  • Kidney Diseases / complications
  • Kidney Diseases / metabolism
  • Liver Diseases / complications
  • Liver Diseases / metabolism
  • Maraviroc
  • Membrane Fusion / drug effects*
  • Receptors, CCR5 / chemistry
  • Receptors, CCR5 / physiology
  • Triazoles / pharmacokinetics
  • Triazoles / pharmacology*
  • Virus Attachment / drug effects*
  • Virus Internalization / drug effects*
  • Virus Replication / drug effects
  • env Gene Products, Human Immunodeficiency Virus / chemistry
  • env Gene Products, Human Immunodeficiency Virus / physiology

Substances

  • CCR5 Receptor Antagonists
  • Chemokines, CC
  • Cyclohexanes
  • Cytochrome P-450 CYP3A Inhibitors
  • HIV Fusion Inhibitors
  • Receptors, CCR5
  • Triazoles
  • env Gene Products, Human Immunodeficiency Virus
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Maraviroc