Fosamprenavir/ritonavir plus tenofovir does not affect amprenavir pharmacokinetics: no effect of tenofovir

Abstract

The effect of tenofovir disoproxil fumarate (TDF) in combination with two boosted fosamprenavir regimens on amprenavir pharmacokinetic parameters was assessed in this prospective phase I crossover study with 30 healthy volunteers. The co-administration of TDF 300 mg once a day with fosamprenavir/ritonavir 1400/200 mg or 1400/100 mg once a day has no effect on the pharmacokinetics of amprenavir and results in non-significant increases of ritonavir pharmacokinetic parameters, suggesting that no dose modification is necessary when combining fosamprenavir/ritonavir with TDF.

Pharmacokinetic Interaction between Fosamprenavir-Ritonavir and Rifabutin in Healthy Subjects

“…Neutropenia (absolute neutrophil count of Ͻ750/mm 3 ) has been found in 25% of subjects receiving RFB in efficacy studies (Mycobutin product information, February 2002) but has not been reported for healthy subjects receiving FPV with or without RTV (4,(6)(7)(8)(9). Therefore, it is likely that the neutropenia observed during this study was related to RFB administration.…”

Steady‐state amprenavir and tenofovir pharmacokinetics after coadministration of unboosted or ritonavir‐boosted fosamprenavir with tenofovir disoproxil fumarate in healthy volunteers

“…In previous TDF-FPV/RTV coadministration studies, the effect of adding an FPV regimen to a TDF regimen was not evaluated. However, two studies that evaluated APV pharmacokinetics following the addition of TDF 300 mg qd to an FPV/RTV 700/100 mg bid or 1400/200 mg qd regimen noted negligible increases in steady-state APV C min values (by 4% [15] and 2% [19], respectively). The Fosamprenavir-tenofovir interaction 195 APV and TFV pharmacokinetic changes observed in our study were unlikely to be clinically important because the steady-state geometric mean TFV C min remained within the range reported in HIV-infected patients treated with TDF 300 mg qd without concurrent FPV [22][23][24], and the geometric mean APV C min for unboosted FPV (0.351 mg/ mL) and FPV/RTV (2.88 mg/mL) during TDF coadministration remained 2.4-and 19.7-fold higher than the documented protein binding-adjusted 50% inhibitory concentration (IC 50 ) for wild-type HIV isolates (0.146 mg/mL), respectively [25].…”

“…Although the combination of TDF with fosamprenavir (FPV), the phosphate ester prodrug of the PI amprenavir (APV), has been reported to be effective and well tolerated in HIV-infected patients [4,[15][16][17][18][19], a formal TDF-FPV drug interaction study has not been carried out to date. The current study was designed to investigate whether there is a drug interaction when TDF 300 mg once daily (qd) is combined with either unboosted FPV 1400 mg twice daily (bid) or an RTV-boosted FPV regimen (FPV/RTV 700/ 100 mg bid).…”

“….2009 (2010), 11, 193-199 193 for TFV increased by 22-32% when TDF was combined with unboosted atazanavir (ATV), ATV boosted by ritonavir (ATV/ RTV), lopinavir (LPV)/RTV, or darunavir (DRV)/RTV, accompanied by 15-20% decreases in ATV and LPV AUCs and a 21% increase in the DRV AUC [10][11][12][13][14]. Although the combination of TDF with fosamprenavir (FPV), the phosphate ester prodrug of the PI amprenavir (APV), has been reported to be effective and well tolerated in HIV-infected patients [4,[15][16][17][18][19], a formal TDF-FPV drug interaction study has not been carried out to date. The current study was designed to investigate whether there is a drug interaction when TDF 300 mg once daily (qd) is combined with either unboosted FPV 1400 mg twice daily (bid) or an RTV-boosted FPV regimen (FPV/RTV 700/ 100 mg bid).…”

Recent developments in the clinical pharmacology of anti-HIV nucleoside analogs

“…In preclinical studies, tenofovir did not inhibit a panel of cytochrome P450 (CYP) enzymes in vitro, including CYP3A4 [30]. A summary of recent drug interaction findings is given in Table 1 [ [31][32][33][34][35][36][37][38].…”