Fozivudintidoxil

Structural formula
General
Non-proprietary name	Fozivudintidoxil
other names	HDP 99.0002; [(2 S , 3 S , 5 R ) -3-azido-5- (5-methyl-2,4-dioxopyrimidin-1-yl) tetrahydrofuran-2-yl] methyl [(2 RS ) -decoxy- 3-dodecylsulfanyl-propyl] hydrogen phosphate ( IUPAC );
Molecular formula	C 35 H 64 N 5 O 8 PS
External identifiers / databases
PubChem	64140
ChemSpider	57716
DrugBank	DB12423
Wikidata	Q1440263
Drug information
Drug class	Antiviral agent , nucleoside reverse transcriptase inhibitors
Mechanism of action	competitive inhibition of reverse transcriptase
properties
Molar mass	745.95 g mol −1
safety instructions
GHS hazard labeling ; no classification available
GHS hazard labeling ; no classification available
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Fozivudintidoxil (manufacturer: Heidelberg-Pharma ; planned trade name: Tidoxil) is an experimental drug for the treatment of HIV- infected patients as part of an HIV combination therapy .

The active ingredient belongs to the group of nucleoside reverse transcriptase inhibitors (NRTIs).

pharmacology

Fozivudintidoxil is a conjugate of azidothymidine (AZT) that is linked to a lipid through a thioether bond . Compared to AZT, fozivudintidoxil is several times more effective in HIV-1 infected CEM-SS cells (a cell line). In-vitro synergistic effects with protease inhibitors have been described, as they also occur with other inhibitors of reverse transcriptase ( HAART ).

Pharmacokinetics

Fozivudintidoxil is selectively distributed through the prodrug formation in various organ systems, especially in the lymphatic tissue , but not in the bone marrow. The concentrations in the blood plasma and in the CSF were comparable.

Fozivudintidoxil has a significantly longer half-life in blood plasma compared to azidothymidine. This means that it can be taken once a day.

Side effects

The development of fozivudintidoxil has been discontinued due to its toxicity to cells of the bone marrow and liver . In a clinical phase II study, one patient discontinued participation due to elevated liver values.

Resistances

Nothing has yet been published about resistance.

Individual evidence

↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
↑ Fozivudine: BM 211290, fozivudine tidoxil, FZT, HDP 990002, W 09726867. In: Drugs in R&D. Volume 5, Number 1, 2004, pp. 41-43, PMID 14725491 .
↑ AC Venhoff, D. Lebrecht, FU Reuss, B. Heckl-Ostreicher, R. Wehr, UA Walker, N. Venhoff: Mitochondrial DNA depletion in rat liver induced by fosalvudine tidoxil, a novel nucleoside reverse transcriptase inhibitor prodrug. In: Antimicrobial agents and chemotherapy. Volume 53, Number 7, July 2009, pp. 2748-2751, doi: 10.1128 / AAC.00364-09 . PMID 19433557 . PMC 2704664 (free full text).
↑ Girard PM, Pegram PS, Diquet B, Anderson R, Raffi F, Tubiana R, Sereni D, Boerner D: Phase II placebo-controlled trial of fozivudine tidoxil for HIV infection: pharmacokinetics, tolerability, and efficany . J Acquir Immune Defic Syndr. 2000 Mar 1; 23 (3): 227-235. PMID 10839658 .

[NV-1] This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.

[2] Fozivudine: BM 211290, fozivudine tidoxil, FZT, HDP 990002, W 09726867. In: Drugs in R&D. Volume 5, Number 1, 2004, pp. 41-43, PMID 14725491 .

[3] AC Venhoff, D. Lebrecht, FU Reuss, B. Heckl-Ostreicher, R. Wehr, UA Walker, N. Venhoff: Mitochondrial DNA depletion in rat liver induced by fosalvudine tidoxil, a novel nucleoside reverse transcriptase inhibitor prodrug. In: Antimicrobial agents and chemotherapy. Volume 53, Number 7, July 2009, pp. 2748-2751, doi: 10.1128 / AAC.00364-09 . PMID 19433557 . PMC 2704664 (free full text).

[4] Girard PM, Pegram PS, Diquet B, Anderson R, Raffi F, Tubiana R, Sereni D, Boerner D: Phase II placebo-controlled trial of fozivudine tidoxil for HIV infection: pharmacokinetics, tolerability, and efficany . J Acquir Immune Defic Syndr. 2000 Mar 1; 23 (3): 227-235. PMID 10839658 .