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Information |
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Drug Groups
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approved |
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Description
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Fosamprenavir is a prodrug of amprenavir, an inhibitor of human immunodeficiency virus (HIV) protease. |
| Indication |
Indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection, as well as postexposure prophylaxis of HIV infection in individuals who have had occupational or nonoccupational exposure to potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission. The use of fosamprenavir is pending revision due to a potential association between the drug and myocardial infarction and dyslipidemia in HIV infected adults. |
| Pharmacology |
Fosamprenavir is a pro-drug of the protease inhibitor and antiretroviral drug amprenavir. It has little or no antiviral activity until it is hydrolyzed by cellular phosphatases into amprenavir, which is the active ingredient. That metabolization increases the duration that amprenavir is available, making fosamprenavir a slow-release version of amprenavir and thus reducing the number of pills required versus standard amprenavir. |
| Affected Organisms |
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Human Immunodeficiency Virus |
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| Biotransformation |
In the gut epithelium during absorption, fosamprenavir is rapidly and almost completely hydrolyzed to amprenavir and inorganic phosphate prior to reaching the systemic circulation. Amprenavir is metabolized in the liver by the cytochrome P450 3A4 (CYP3A4) enzyme system. |
| Absorption |
The absolute oral bioavailability of amprenavir after administration of fosamprenavir in humans has not been established. After administration of a single 1,400 mg dose in the fasted state, fosamprenavir oral suspension (50 mg/mL) and fosamprenavir tablets (700 mg) provided similar amprenavir exposures (AUC), however, the Cmax of amprenavir after administration of the suspension formulation was 14.5 % higher compared with the tablet. |
| Half Life |
The plasma elimination half-life of amprenavir (the active metabolite) is approximately 7.7 hours. |
| Protein Binding |
Very high (approximately 90%); primarily bound to alpha 1 -acid glycoprotein. Higher amounts of unbound amprenavir present as amprenavir serum concentrations increase. |
| Elimination |
Excretion of unchanged amprenavir in urine and feces is minimal. The renal elimination of unchanged amprenavir represents approximately 1% of the administered dose; therefore, renal impairment is not expected to significantly impact the elimination of amprenavir. Amprenavir, the active metabolite of fosamprenavir, is metabolized in the liver by the cytochrome P450 enzyme system. |
| References |
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Smith KY, Weinberg WG, Dejesus E, Fischl MA, Liao Q, Ross LL, Pakes GE, Pappa KA, Lancaster CT: Fosamprenavir or atazanavir once daily boosted with ritonavir 100 mg, plus tenofovir/emtricitabine, for the initial treatment of HIV infection: 48-week results of ALERT. AIDS Res Ther. 2008 Mar 28;5:5.
[Pubmed]
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Hoffman RM, Umeh OC, Garris C, Givens N, Currier JS: Evaluation of sex differences of fosamprenavir (with and without ritonavir) in HIV-infected men and women. HIV Clin Trials. 2007 Nov-Dec;8(6):371-80.
[Pubmed]
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Chapman TM, Plosker GL, Perry CM: Fosamprenavir: a review of its use in the management of antiretroviral therapy-naive patients with HIV infection. Drugs. 2004;64(18):2101-24.
[Pubmed]
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Furfine ES, Baker CT, Hale MR, Reynolds DJ, Salisbury JA, Searle AD, Studenberg SD, Todd D, Tung RD, Spaltenstein A: Preclinical pharmacology and pharmacokinetics of GW433908, a water-soluble prodrug of the human immunodeficiency virus protease inhibitor amprenavir. Antimicrob Agents Chemother. 2004 Mar;48(3):791-8.
[Pubmed]
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Sension M: Initial therapy for human immunodeficiency virus: broadening the options. HIV Clin Trials. 2004 Mar-Apr;5(2):99-111.
[Pubmed]
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Wood R, Arasteh K, Stellbrink HJ, Teofilo E, Raffi F, Pollard RB, Eron J, Yeo J, Millard J, Wire MB, Naderer OJ: Six-week randomized controlled trial to compare the tolerabilities, pharmacokinetics, and antiviral activities of GW433908 and amprenavir in human immunodeficiency virus type 1-infected patients. Antimicrob Agents Chemother. 2004 Jan;48(1):116-23.
[Pubmed]
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Falcoz C, Jenkins JM, Bye C, Hardman TC, Kenney KB, Studenberg S, Fuder H, Prince WT: Pharmacokinetics of GW433908, a prodrug of amprenavir, in healthy male volunteers. J Clin Pharmacol. 2002 Aug;42(8):887-98.
[Pubmed]
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Wire MB, Shelton MJ, Studenberg S: Fosamprenavir : clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clin Pharmacokinet. 2006;45(2):137-68.
[Pubmed]
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