Stavudine

J05AF04

Antiviral agent, nucleoside reverse transcriptase inhibitors

Competitive inhibition of reverse transcriptase

Soluble in water (6.6 g · l-1 at 25 ° C)

1000 mg · kg -1 ( LD50, mouse, oral)

Template: Infobox chemical / molecular formula search available

Stavudine ( d4T ) (trade name: Zerit ®, manufactured by Bristol -Myers Squibb ) is a drug used to treat infected with HIV-1 patients as part of a combination antiretroviral therapy.

It belongs to the group of the nucleoside reverse transcriptase - inhibitor (NRTI ).

Properties

Stavudine can occur in four different crystal forms. The polymorphic forms I, II and IV are different based on their melting points with 168.1 ° C, 165.5 ° C and 169.5 ° C. Form I is the thermodynamically stable form at room temperature. In Form III is 1/3-Hydrat with a stoichiometric ratio of active ingredient to water of 3: 1 in the crystal lattice.

Pharmacology

In vitro antiretroviral activity of stavudine was demonstrated. The substance is in vitro 5-10 times weaker than zidovudine. In combination with other antiviral agents synergistic effects could be detected. The development of stavudine - resistant HIV viruses has been demonstrated in vitro.

Pharmacokinetics

The bioavailability of stavudine is good. Approximately 90 % is absorbed orally. Coadministration with food has only small, clinically insignificant, effect. Following administration of 40 mg, peak concentrations of approximately 0.8-1.0 mg / l can be achieved in the plasma. CSF concentrations: up to 70 % of plasma concentrations. Elimination half-life: about 1.6 hours. Intracellular half-life of biologically active triphosphate: about 3.5 hours.

Side effects

Strong mitochondrial toxicity. Lipoatrophy. Peripheral neuropathy ( PNP), especially in combination with ddI. Rarely, diarrhea, nausea, headache. Hepatic steatosis, pancreatitis. Very rare: lactic acidosis. No combination with AZT, due to antagonism. Contraindicated in PNP. Neurotoxic drugs avoid ( ethambutol, cisplatin, INH, vincristine, etc.).

Development

The substance was synthesized in 1966 by Jerome P. Horwitz.