Фосампренавир кальций

Описание

Fosamprenavir, a prodrug of the HIV protease inhibitor amprenavir, is indicated for the oral treatment of HIV infection in adults in combination with other antiretroviral agents. Although amprenavir has excellent antiviral potency and good tolerability, its watersolubility is poor (0.04 mg/ml). As a result, the formulation of the agent includes a high percentage of organic excipients to facilitate gastric dissolution, which limits the amount of active drug that can be formulated per capsule. Fosamprenavir is a highly soluble phosphate ester of amprenavir. It allows more convenient dosing and reduction in pill counts as compared to amprenavir. Fosamprenavir is readily prepared in two steps starting from a key intermediate used in the synthesis of amprenavir, by phosphorylating a hydroxyl group and subsequently reducing a p-nitrophenyl to a p-aminophenyl group. Fosamprenavir has little or no antiviral activity in vitro. After oral administration, it is rapidly and almost completely hydrolyzed by phosphatases in the gut epithelium to amprenavir prior to reaching systemic circulation. The time to reach peak plasma concentration of amprenavir is approximately 2.5 h and the plasma elimination half-life is approximately 7.7 h. Amprenavir is metabolized in the liver by CYP3A4 and ＞90% of the dose is excreted as metabolites in urine and feces. In most patients, fosamprenavir is administered at daily doses of 700–1400 mg in conjunction with ritonavir. Monotherapy with fosamprenavir is only recommended in antiretroviral therapy-na?ve patients and the dosing regimen is 1400 mg twice daily. The most common adverse events experienced with fosamprenavir are diarrhea, nausea, vomiting, headache and rash.

Химические свойства

White Microcrystalline Needles

Общее описание

Fosamprenavir is used in combination with otherHIV drugs in adult patients. Like the other PIs, this compoundis a prodrug that produces the active drug uponhydrolysis. In this case, the active drug is amprenavir, apeptidomimetic transition state inhibitor. Fosamprenaviris typically administered in combination with RTinhibitors.

Клиническое использование

Fosamprenavir calcium has been approved for the treatment of HIV in adults when used in combination with other anti-HIV drugs. It is a prodrug that, on hydrolysis by serum phosphatases, gives rise to amprenavir, which is a peptidomimetic transition-state inhibitor that targets HIV-1 protease and reduces the viral replication and, thus, the infectiousness of HIV-1. It is commonly administered in combination with RT inhibitors to produce excellent efficacy in patients with AIDS. The drug is administered as two 700 mg tablets twice daily or, in combination with ritonavir, can be given as two 700 mg tables once daily or one 700 mg tablet twice daily. As a result, formaprenavir lowers the "pill burden" in patients with AIDS.