Drug interaction between amprenavir and lopinavir/ritonavir in salvage therapy

Clinical Impact of Double Protease Inhibitor Boosting with Lopinavir/Ritonavir and Amprenavir as Part of Salvage Antiretroviral Therapy

“…[8][9][10][11][12][13][14][15][16][17][18] Different studies showed that APV levels were either decreased, unchanged, or increased and LPV levels were either decreased or unchanged. [8][9][10][11][12][13][14][15][16][17][18] However, these studies are limited to PK analysis, involve small numbers of patients or healthy volunteers, are retrospective in design, and typically compared their results to historical controls. In contrast, a recent in vitro study suggested that the combination of APV and LPV/r resulted in additive inhibition of wild-type virus.…”

“…Although there have been many in vitro studies on the PK interaction of APV and LPV/r, there have been no data on the virologic response or clinical outcome of double boosting with these two PIs. [8][9][10][11] The PK studies on the drug interaction between LPV/r and APV are conflicting, which results in a poor understanding of how best to use these two PIs in combination in clinical practice. [8][9][10][11] The in vitro data suggest that both LPV and APV can induce cytochrome p450 3A4 enzyme activity, providing a mechanism by which each PI lowers the level of the other when used in combination; this potential two-way drug interaction could result in a poorer virologic response.…”

“…[8][9][10][11] The PK studies on the drug interaction between LPV/r and APV are conflicting, which results in a poor understanding of how best to use these two PIs in combination in clinical practice. [8][9][10][11] The in vitro data suggest that both LPV and APV can induce cytochrome p450 3A4 enzyme activity, providing a mechanism by which each PI lowers the level of the other when used in combination; this potential two-way drug interaction could result in a poorer virologic response. [8][9][10][11] The PK studies have shown that APV minimum concentration (C min ) is either lowered by 33%-81% or is unchanged when combined with LPV/r.…”

“…[8][9][10][11] The in vitro data suggest that both LPV and APV can induce cytochrome p450 3A4 enzyme activity, providing a mechanism by which each PI lowers the level of the other when used in combination; this potential two-way drug interaction could result in a poorer virologic response. [8][9][10][11] The PK studies have shown that APV minimum concentration (C min ) is either lowered by 33%-81% or is unchanged when combined with LPV/r. [8][9][10][11][12][13][14][15][16][17][18] Some studies have shown that LPV levels were decreased by simultaneous use with APV, whereas other studies found that LPV levels were not lowered by APV.…”

“…[8][9][10][11] The PK studies have shown that APV minimum concentration (C min ) is either lowered by 33%-81% or is unchanged when combined with LPV/r. [8][9][10][11][12][13][14][15][16][17][18] Some studies have shown that LPV levels were decreased by simultaneous use with APV, whereas other studies found that LPV levels were not lowered by APV. 8,[13][14][15][16][17][18] Given these data, it remains unclear whether the doses of the two PIs should be increased when used in combination.…”