| InChI | InChI=1S/C25H36N3O9PS/c1-18(2)15-28(39(33,34)22-10-8-20(26)9-11-22)16-24(37-38(30,31)32)23(14-19-6-4-3-5-7-19)27-25(29)36-21-12-13-35-17-21/h3-11,18,21,23-24H,12-17,26H2,1-2H3,(H,27,29)(H2,30,31,32)/t21-,23-,24+/m0/s1 |
| Reference | 1. Clin Pharmacokinet. 2006;45(2):137-68. <br />
Fosamprenavir : clinical pharmacokinetics and drug interactions of the amprenavir
prodrug. <br />
Wire MB(1), Shelton MJ, Studenberg S. <br />
Author information: <br />
(1)Division of Clinical Pharmacology & Discovery Medicine (CPDM),
GlaxoSmithKline, Research Triangle Park, North Carolina, USA. [email protected] <br />
Fosamprenavir is one of the most recently approved HIV-1 protease inhibitors
(PIs) and offers reductions in pill number and pill size, and omits the need for
food and fluid requirements associated with the earlier-approved HIV-1 PIs. Three
fosamprenavir dosage regimens are approved by the US FDA for the treatment of
HIV-1 PI-naive patients, including fosamprenavir 1,400 mg twice daily,
fosamprenavir 1,400 mg once daily plus ritonavir 200mg once daily, and
fosamprenavir 700 mg twice daily plus ritonavir 100mg twice daily.
Coadministration of fosamprenavir with ritonavir significantly increases plasma
amprenavir exposure. The fosamprenavir 700 mg twice daily plus ritonavir 100mg
twice daily regimen maintains the highest plasma amprenavir concentrations
throughout the dosing interval; this is the only approved regimen for the
treatment of HIV-1 PI-experienced patients and is the only regimen approved in
the European Union. Fosamprenavir is the phosphate ester prodrug of the HIV-1 PI
amprenavir, and is rapidly and extensively converted to amprenavir after oral
administration. Plasma amprenavir concentrations are quantifiable within 15
minutes of dosing and peak at 1.5-2 hours after fosamprenavir dosing. Food does
not affect the absorption of amprenavir following administration of the
fosamprenavir tablet formulation; therefore, fosamprenavir tablets may be
administered without regard to food intake. Amprenavir has a large volume of
distribution, is 90% bound to plasma proteins and is a substrate of
P-glycoprotein. With <1% of a dose excreted in urine, the renal route is not an
important elimination pathway, while the principal route of amprenavir
elimination is hepatic metabolism by cytochrome P450 (CYP) 3A4. Amprenavir is
also an inhibitor and inducer of CYP3A4. Furthermore, fosamprenavir is commonly
administered in combination with low-dose ritonavir, which is also extensively
metabolised by CYP3A4, and is a more potent CYP3A4 inhibitor than amprenavir.
This potent CYP3A4 inhibition contraindicates the coadministration of certain
CYP3A4 substrates and requires others to be co-administered with caution.
However, fosamprenavir can be co-administered with many other antiretroviral
agents, including drugs of the nucleoside/nucleotide reverse transcriptase
inhibitor, non-nucleoside reverse transcriptase inhibitor and HIV entry inhibitor
classes. Coadministration with other HIV-1 PIs continues to be studied.The
extensive fosamprenavir and amprenavir clinical drug interaction information
provides guidance on how to co-administer fosamprenavir and fosamprenavir plus
ritonavir with many other commonly co-prescribed medications, such as gastric
acid suppressants, HMG-CoA reductase inhibitors, antibacterials and antifungal
agents. <br />
2. J HIV Ther. 2004 Nov;9(4):87-91. <br />
Pharmacokinetics of Telzir (fosamprenavir). <br />
Wilkins E(1). <br />
Author information: <br />
(1)Department of Infectious Diseases, North Manchester General Hospital,
Delaunays Road, Manchester M8 5RB, UK. <br />
Fosamprenavir is a recently licensed protease inhibitor (PI) for the treatment of
patients with HIV. It has potent antiviral activity when boosted by ritonavir and
produces durable virological suppression when combined with other antiretroviral
drugs. In addition, it is well tolerated with a good safety profile, and can be
taken once or twice daily with no food restrictions. Trough plasma levels
obtained with once or twice daily boosted fosamprenavir are above the mean
protein-binding adjusted IC50 values for wild-type and PI-resistant virus. When
given twice daily boosted, no significant pharmacokinetic (PK) interaction is
seen with tenofovir, the nucleoside reverse transcriptase inhibitors (NRTIs),
efavirenz or nevirapine, and there is no requirement for any dose adjustment.
Interactions with other PIs are difficult to predict. A reduction in plasma
amprenavir level is seen when fosamprenavir or amprenavir is combined with
ritonavir-boosted lopinavir, saquinavir or tipranavir: reductions in lopinavir
and saquinavir plasma levels are also seen. Various dosing strategies have been
evaluated to overcome these negative interactions. With unboosted atazanvir, an
increase in amprenavir levels is found. This article will focus on the
pharmacokinetics of ritonavir-boosted fosampreanvir and review drug interactions
with other antiretroviral (ARV) and non-ARV agents. <br />
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