Tipranavir

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Structural formula
Tipranavir structural formula
General
Non-proprietary name Tipranavir
other names

N - [3 - [(1 R ) -1 - [(2 R ) -6-hydroxy-4-oxo-2- (2-phenylethyl) -2-propyl-3 H -pyran-5-yl] propyl] phenyl] -5- (trifluoromethyl) pyridine-2-sulfonamide ( IUPAC )

Molecular formula C 31 H 33 F 3 N 2 O 5 S
External identifiers / databases
CAS number
  • 174484-41-4 (tipranavir)
  • 191150-83-1 (tipranavir disodium salt)
EC number 629-839-6
ECHA InfoCard 100.158.066
PubChem 54682461
DrugBank DB00932
Wikidata Q423404
Drug information
ATC code

J05 AE09

Drug class

HIV protease inhibitor

properties
Molar mass 584.73 g · mol -1
Physical state

firmly

Melting point

86-89 ° C

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
09 - Dangerous for the environment
H and P phrases H: 411
P: ?
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Tipranavir (TPV, trade name: Aptivus ® , manufacturer: Boehringer Ingelheim ) is a drug for the treatment of HIV-1 infected patients as part of a combination antiretroviral therapy . It belongs to the group of HIV protease inhibitors , but differs structurally from the other representatives of this class. An oral dosage form was approved in the USA and Europe in 2005.

Indication and effect

Tipranavir for the treatment of HIV infection in individuals against other HIV protease inhibitors resistant , developed are. Due to possible serious side effects , the approval was granted “under special conditions” ( European Medicines Agency ). Tipranavir should usually be taken in combination with ritonavir . Treatment with HIV protease inhibitors takes place within the framework of a "highly active antiretroviral therapy" ( HAART ) in conjunction with other drugs, so-called reverse transcriptase inhibitors ( NNRTI , NRTI ).

Mechanism of action and pharmacokinetics

HIV protease inhibitors block an enzyme that the virus needs to produce infectious new virus particles. The result is a lowering of the viral load . In some cases, however, resistances to these active ingredients develop relatively quickly. In contrast to the other representatives of the HIV protease inhibitors, tipranavir does not have a peptide- like structure. It is thus the first representative of the non-peptide HIV protease inhibitors. The differences in the structure obviously mean that this drug is less subject to cross-resistance than the peptide HIV protease inhibitors and thus also acts against HIV strains that have already developed resistance to other therapeutic agents. In such strains, studies have shown significantly better efficacy of tipranavir than other HIV protease inhibitors. Tipranavir is taken with a meal twice a day. Tipranavir is more than 90% bound to proteins in the blood . The drug is largely broken down in the liver via the cytochrome P450 enzyme system, mainly the isoenzyme CYP3A4, and excreted in the stool. The mean plasma half-life of tipranavir is approximately five to six hours.

Side effects and risks

The better effectiveness of tipranavir compared to the other representatives of the HIV protease inhibitors is apparently associated with a greater risk of side effects. The treatment discontinuation rate in the clinical studies in the patients treated with tipranavir was 8% and thus twice as high as in the comparison group (4%). Diarrhea and nausea are the most common . There is also headache, abdominal pain and skin rashes. The combination of tipranavir / ritonavir could be toxic to the liver, especially in combination with enfuvirtide. Elevated levels of transaminases are relatively common. Therefore, tipranavir must not be used in patients with moderate or severe liver failure .

The interaction profile of tipranavir in combination with ritonavir is complex. Responsible for this is a complicated mechanism of induction and inhibition of various metabolic mechanisms in the organism (for example cytochrome P450). The antituberculotic drug rifampicin , the cholesterol-lowering drugs lovastatin and simvastatin must not be used at the same time . Atorvastatin is allowed with restrictions. Certain benzodiazepines , oral contraceptives and the antibiotic clarithromycin, as well as other antiretroviral agents, also change the plasma level of tipranavir.

Web links

literature

  • KS Fors et al.: A Convergent Scalable Synthesis of HIV Protease Inhibitor PNU-140960. In: J Org Chem. 63 (21), Oct 16, 1998, pp. 7348-7356. PMID 11672382 .
  • SM Poppe, DE Slade, KT Chong, RR Hinshaw, PJ Pagano, M. Markowitz, DD Ho, H. Mo, RR Gorman, TJ Dueweke, S. Thaisrivongs, WG Tarpley: Antiviral activity of the dihydropyrone PNU-140690, a new nonpeptidic human immunodeficiency virus protease inhibitor. In: Antimicrob. Agents Chemother. 41 (5), 1997, pp. 1058-1063. PMID 9145869 .

Individual evidence

  1. ^ The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition. 2006, ISBN 0-911910-00-X , p. 1626.
  2. Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of N- {3 - [(1R) -1 - [(6R) -4-hydroxy-2-oxo-6- (2-phenylethyl) -6-propyl-5, derived from a self-classification by the distributor , is shown, 6-dihydro-2H-pyran-3-yl] propyl] phenyl} -5- (trifluoromethyl) pyridine-2-sulfonamide in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on July 19, 2019.