Maraviroc

from Wikipedia, the free encyclopedia
Structural formula
Structure of Maraviroc
General
Non-proprietary name Maraviroc
Molecular formula C 29 H 41 F 2 N 5 O
External identifiers / databases
CAS number 376348-65-1
EC number 609-456-0
ECHA InfoCard 100.124.927
PubChem 3002977
DrugBank DB04835
Wikidata Q421369
Drug information
ATC code

J05 AX09

Drug class

Entry inhibitor

Mechanism of action

CR5 coreceptor antagonist

properties
Molar mass 513.67 g · mol -1
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
08 - Dangerous to health

Caution

H and P phrases H: 373-412
P: ?
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Maraviroc (MVC, trade name: Celsentri , manufacturer: Pfizer ) is a complex chemical compound that is used as a drug to treat HIV infections and their consequences. It belongs to the group of entry inhibitors (coreceptor antagonists).

pharmacology

Maraviroc is an entry inhibitor that, as a selective inhibitor, blocks the human chemokine receptor CCR5 and thus prevents the docking of HI viruses on human cells, especially macrophages . The cell is not infected. However, its effect is limited to (R5) HI viruses using CCR5. With the help of bioinformatic methods, it is now possible to distinguish HI viruses using CCR5 from HI viruses using CXCR4 with a very high degree of accuracy.

Pharmacokinetics

Maraviroc is absorbed from the gastrointestinal tract. The recommended dose is 150, 300 or 600 mg twice a day, depending on the rest of the HAART , which interacts more or less with the behavior of maraviroc. The bioavailability is 23 to 33%. The drug can be taken with or without food. 76% of the active substance is bound to plasma proteins, the volume of distribution was calculated to be 2.8 ± 0.9 l / kg.

Maraviroc is metabolized by cytochrome P450 monooxygenases . A relevant inductive or inhibitory effect was not demonstrated. The most important metabolic product is a metabolite dealkylated on nitrogen. The substance is mainly excreted in the stool (approx. 25% unchanged); 8% of a 300 mg dose appears unchanged in the urine. After intravenous administration, the elimination half-life is approx. 13 hours.

In patients with congenital or drug-induced renal insufficiency, a dose adjustment may be necessary (inclusion of the other HAART drugs). With mild or moderate impairment of the liver function, the blood levels are increased by approx. 25 to 46%. Sufficient data are not yet available for this group of patients. Studies in children and the elderly have not yet been conducted.

Side effects

Diarrhea, general malaise, stomach pain, gas, loss of appetite, headache, insomnia, depression, rash, feeling weak or weak, anemia and an increase in liver enzymes are the most frequently reported adverse events. In addition, life-threatening skin reactions and allergic reactions as well as liver diseases can occur. Furthermore, serious side effects are known from an interaction with grapefruit.

Off-label use

Maraviroc has been reported to be effective against progressive multifocal leukoencephalopathy associated with immune reconstitution syndrome. The effect is attributed to the immunomodulatory properties of maraviroc. So far there have been no studies on the subject. Maraviroc is being considered as a potential drug for COVID-19 .

Individual evidence

  1. ↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . What is shown is a label for 4,4-difluoro-N - [(1S) -3 - [(1R, 5S) -3- (3-methyl-5-propan-2-yl-1, 2,4-triazol-4-yl) -8-azabicyclo [3.2.1] octan-8-yl] -1-phenylpropyl] cyclohexane-1-carboxamide in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on 7 July 2020.
  2. ^ AIDS Meds - American HIV Drugs Website .
  3. ↑ Jan Nikolaj Dybowski, Dominik Heider , Daniel Hoffmann: Prediction of Co-Receptor Usage of HIV-1 from Genotype . In: PLoS Computational Biology . 6, No. 4, April 15, 2010, p. E1000743. doi : 10.1371 / journal.pcbi.1000743 . Retrieved November 26, 2012.
  4. ↑ a b Celsentri film-coated tablets: Instructions for use for users. ViiV Healthcare, May 2020, accessed August 11, 2020 .
  5. ↑ Drug overdose from grapefruit
  6. ^ Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents .
  7. ↑ Glecaprevir and Maraviroc are high-affinity inhibitors of SARS-CoV-2 main protease: possible implication in COVID-19 therapy, Shamsi et al., In: Bioscience Reports, Volume 40, Issue 6, June 2020

Web links