Raltegravir

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models Raltegravir, better known as Isentress, ([[___]]) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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.^[1]
• The following is a list of Pharmacokinetic Parameters. See: Pharmaceutical Drugs for more information

Mechanism of Action

Pharmacokinetics

Retroviral Integrase Inhibitor Pharmacokinetics [2][3]
Parameter	Raltegravir	Elvitegravir
Tmax (hr)	1.8	2-4
Cmax (ng/ml)	4253	2070
Bioavailability (%)	32	~30
Protein Binding (%)	83	N/A
T1/2 (hr)	10.8	7.6
AUC (ng/ml/hr)	10168	21200
Dosage (mg)	400	150
Metabolism	Hepatic - (UGT1A1)	Hepatic - (CYP3A4)

References

1. ↑ Steigbigel RT, Cooper DA, Kumar PN, Eron JE, Schechter M, Markowitz M, Loutfy MR, Lennox JL, Gatell JM, Rockstroh JK, Katlama C, Yeni P, Lazzarin A, Clotet B, Zhao J, Chen J, Ryan DM, Rhodes RR, Killar JA, Gilde LR, Strohmaier KM, Meibohm AR, Miller MD, Hazuda DJ, Nessly ML, DiNubile MJ, Isaacs RD, Nguyen BY, Teppler H. Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med. 2008 Jul 24;359(4):339-54. PMID:18650512 doi:10.1056/NEJMoa0708975
2. ↑ A Gaur, et al. Pharmacokinetics and Safety of Once-Daily Elvitegravir in HIV-Infected Adolescents. 17th Conference on Retroviruses. Poster Number: 874.
3. ↑ Iwamoto M, Wenning LA, Petry AS, Laethem M, De Smet M, Kost JT, Breidinger SA, Mangin EC, Azrolan N, Greenberg HE, Haazen W, Stone JA, Gottesdiener KM, Wagner JA. Minimal effects of ritonavir and efavirenz on the pharmacokinetics of raltegravir. Antimicrob Agents Chemother. 2008 Dec;52(12):4338-43. Epub 2008 Oct 6. PMID:18838589 doi:10.1128/AAC.01543-07