Important note: Information in this article was accurate in August 2000. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, August 7, 2000
Prepared by AIDS Weekly editors from staff and other reports
NewsRx -- The new protease inhibitor (PI) Amprenavir , which recently received marketing approval from the U.S. Food and Drug Administration, can be used in both initial and salvage combination therapies.
"Amprenavir is a potent competitive inhibitor of HIV-1 protease and a relatively weak inhibitor of HIV-2 protease. Inhibition of the HIV-1 protease enzyme results in immature and noninfectious viral particles," said H.B. Fung and colleagues, Bronx Veterans Administration Medical Center, New York ("Amprenavir: A new human immunodeficiency virus type 1 protease inhibitor," Clin Ther 2000 May;22(5):549-72.
According to the researchers, Amprenavir is rapidly absorbed to the blood stream following oral administration. The clinical data showed that the time to peak concentration (T-max) in adults was between one and two hours.
"The area under the plasma concentration versus time curve is roughly proportional to the dose, the half-life is similar to eight hours, and the volume of distribution is similar to 430 L," said Fung et al. "The T-max in children four to 12 years of age is between 1.1 and 1.4 hours. The bioavailability of the solution is 86% relative to the capsule formulation. It is metabolized by the cytochrome P-450 isozyme CYP3A4 and to a lesser extent by CYP2D6 and CYP2C9."
Studies reported in the literature indicate that Amprenavir is efficacious in the treatment of HIV disease in patients with primary HIV infection, the researchers noted. It also has been shown efficacious in antiretroviral-naive patients, protease inhibitor-naive patients, protease inhibitor-experienced patients, and pediatric HIV patients.
Any adverse effects usually appeared early (range, two to 21 days) and were transient (range, three to 46 days). So far, metabolic abnormalities such as lipodystrophy, hyperlipidemia, and diabetes mellitus have not yet been reported from use of this drug.
"Amprenavir should be avoided in patients with a known sulfonamide allergy," recommended Fung et al. "Concomitant use of other medications that are CYP3A4 inducers or inhibitors should be done cautiously and only if the potential benefit clearly outweighs potential risk."
The researchers suggested that the dose be reduced in patients with significant hepatic impairment (Child-Pugh score, greater than or equal to5). They also suggested that Amprenavir not be administered with rifabutin, rifampin, astemizole, midazolam, triazolam, bepridil, dihydroergotamine, ergotamine, or cisapride.
Currently, the recommended dose of Amprenavir for adults is 1,200 mg twice daily. For HIV patients between four and 12 years of age or between 13 and 16 years of age who weigh <50 kg, the recommended dosage of the capsule form is 20 mg/kg (22.5 mg/kg for oral solution) twice daily or 15 mg/kg (17 mg/kg for oral solution) three times a day to a maximum dose of 2,400 mg (2,800 mg for oral solution).
"Patients should not take vitamin E supplements because amprenavir is formulated with a large amount of vitamin E (109 IU/capsule and 46 IU/mL oral solution) to improve oral absorption," Fung and colleagues wrote. "Amprenavir may be administered with or without food, but a high-fat meal (>67 g fat) should be avoided.
"Published clinical data are limited, but Amprenavir appears to be efficacious and generally well tolerated in patients with HIV infection. Pharmacoeconomic data are not yet available. The introduction of Amprenavir appears to be important, since it provides an additional treatment option as a component of both initial and salvage combination therapies for patients with HIV."
For additional information, contact H.B. Fung, Bronx Veterans Administration Medical Center, Serv Pharm, 130 W Kingsbridge Rd., Bronx, New York 10468, USA.
A search of the www.NewsRx.com online database using the terms "HIV" and "protease inhibitor" generated 489 articles.
Key points reported in this study are:
This article was prepared by AIDS Weekly editors from staff and other reports.
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