Raltegravir

spinqualitylabelsall models Raltegravir, better known as Isentress, (3l2v) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Better Known as: Isentress Marketed By: Merck & Co. Major Indication: Human Immunodeficiency Virus Infection Drug Class: Retroviral Integrase Inhibitor FDA Approval (Patent Expiration): 2007 (2022) 2009 Sales: ~$1.1 Billion Importance: It was the first drug of the Integrase Inhibitor class to be approved by the FDA. It offers a powerful new tool to be utilized in combination therapies against HIV infections. See Pharmaceutical Drugs for more information about other drugs and disorders. Mechanism of Action Retroviral Integrase is produced by the HIV retrovirus, enabling HIV to integrate its genetic material into the DNA of the infected cell. This integration step effectively transforms the infected cell into a permanent carrier of the viral genome, allowing the virus to persist and proliferate extensively. HIV retroviral integrase forms "intasomes" when it complexes with viral DNA. The integrase domains interact extensively with the viral DNA, binding the nucleotide chains precisely within an active site, in close proximity to the predicted target DNA into which the viral DNA will be inserted. Raltegravir binds with great specificity to the HIV integrase active site. It orients itself in such a way as to displace the reactive viral DNA end from the active site almost completely. Raltegravir binds to residues Asp 128, Asp 185, & Glu 221 via hydrogen bonds, has extensive π-stacking interactions with residues Tyr 212, Pro 214 and the final two nucleotide rings on one viral DNA strand. This disruption prevents the viral DNA from interacting with the target DNA, preventing integration and HIV proliferation.

Pharmacokinetics

Retroviral Integrase Inhibitor Human Immunodeficiency Virus Parameter Raltegravir Retroviral Integrase HIV Pharmaceutical Drugs (hr) 1.8 2-4 N/A Retroviral Integrase (ng/ml) 4253 2070 N/A HIV (%) 32 ~30 N/A DNA (%) 83 N/A N/A T1/2 (hr) 10.8 7.6 N/A AUC (ng/ml/hr) 10168 21200 N/A Dosage (mg) 400 150 N/A Metabolism Hepatic - (UGT1A1) Hepatic - (CYP3A4) N/A For Pharmacokinetic Data References, See: References

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