Efavirenz

(4S )-6- chloro-4 -(2- cyclopropylethinyl ) - 4 - (trifluoromethyl) - 1H-3 ,1 -benzoxazin- 2-one

J05AG03

Antiviral, non-nucleoside reverse transcriptase inhibitors

Non- competitive inhibition of reverse transcriptase

139-141 ° C

Template: Infobox chemical / molecular formula search available

Efavirenz ( EFV, Sustiva ® trade name, Stocrin ®, manufactured by Bristol -Myers Squibb ) is a chiral drug for the treatment of HIV -1 -infected patients under antiretroviral combination therapy.

Efavirenz belongs to the group of non-nucleoside reverse transcriptase inhibitors ( NNRTI) and is used as a pure enantiomer.

Production

The multistep synthesis of efavirenz, including the resolution of an intermediate, is described in the literature.

Pharmacodynamics

Efavirenz belongs to the class of non-nucleoside reverse transcriptase inhibitors. The drug binds non- competitively to the reverse transcriptase of HIV-I, near the substrate binding site for nucleosides. Wherein the catalytically active site is blocked. It can bind only a few nucleosides and the polymerization is slowed significantly.

Pharmacokinetics

The maximum plasma concentration is reached after about 5 hours. Food intake has no effect on the absorption in the rule. The exception are very high fat meals, which increase the absorption by an average of 50%. Plasma protein binding of > 99%. The CSF concentration is about three times as high as the free efavirenz concentration in plasma. The half-life is between 40 to 55 hours. Excretion is about 14-34 % in the urine as metabolites and 16-61 % in the faeces as unchanged drug.

Contraindications

In pregnancy or infertility of the patients Efavirenz should not be used for therapy, as it is teratogenic.

Side effects

Efavirenz may cause psychosis central nervous system side effects such as insomnia, anxiety and nightmares and psychiatric symptoms as well.