Ritonavir Enfuvirtide

Lalezari JP, DeJesus E, Northfelt DW, Richmond G, Wolfe P, Haubrich R, Henry D, Powderly W, Becker S, Thompson M, Valentine E, Wright D, Carlson M, Riddler S, Haas FF, DeMasi R, Sista PR, Salgo M, Delehanty J (2003a) A controlled Phase II trial assessing three doses of enfuvirtide (T-20) in combination with abacavir, amprenavir, ritonavir and efavirenz in nonnucleoside reverse transcriptase inhibitor-naive HIV-infected adults. Antivir Ther 8 279-287... 

Raltegravir, or Isentress (1), is the first FDA-approved inhibitor of HIV integrase. HIV/AIDS drugs are categorized according to their mode of action as nucleoside and nucleotide reverse transcriptase inhibitors [NRTIs, e.g., tenofovir (2)], nonnucleotide reverse transcriptase inhibitors [NNRTIs, e.g., efavirenz (3)] protease inhibitors [Pis, e.g., ritonavir (4)], fusion inhibitors [e.g., enfuvirtide (5)], entry inhibitors... 

Enfuvirtide is not metabolized to a significant extent and is not known to alter the concentrations of any coadministered drugs. Ritonavir, rifampin, or ritonavir plus saquinavir did not alter enfuvirtide concentrations. 

The fusion inhibitor, enfuvirtide, is a peptide. It does not eause eyto-chrome P450-mediated drug interactions, and is not affected by potent enzyme inducers (rifampicin) or inhibitors (ritonavir). 

Ritonavir caused a minor increase in enfuvirtide exposure, which is not clinically relevant. Saquinavir/ritonavir had little effect on enfuvirtide. 

Subcutaneous enfuvirtide 90 mg twice daily was given for 7 days to 24 HIV-positive subjects with either ritonavir 200 mg twice daily or saquinavir/ritonavir 1 g/100 mg twice daily given for the last 4 days. Ritonavir caused a minor 24% increase in the AUC of enfuvirtide, and saquinavir/ritonavir caused a 14% increase in the AUC of enfuvirtide. Such small increases in enfuvirtide exposure are not clinically relevant. No special precautions appear warranted during concurrent use. ... 

Ruxrungdiam K, Boyd M, Bellibas SE, Zhang X, Dorr A, Kolis S, Kinchelow T, Buss N, I tel IH. Lack of interaction between enfuvirtide and ritonavir or ritonavir-boosted saquinavir in HIV-1-infected patients. J Clin Pharmacol (2004) 44, W3-802. 

Tipranavir + ritonavir Co-administration of enfuvirtide with tipranavir + ritonavir was associated with markedly higher tipranavir and ritonavir trough concentrations [220=]. 

Gonz ilez de Requena D, Calcagno A, Bonora S, Ladetto L, D Avolio A, Sciandra M, Siccardi M, Bargiacchi O, Sinicco A, Di Perri G. Unexpected drug-dmg interaction between tipranavir/ritonavir and enfuvirtide. AIDS 2006 20(15) 1977-9. 

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