25495
document
Pharmacokinetic and safety evaluation of high-dose combinations of fosamprenavir and ritonavir . High-dose combinations of fosamprenavir ( FPV ) and ritonavir ( RTV ) were evaluated in healthy adult subjects in order to select doses for further study in multiple protease inhibitor ( PI ) -experienced patients infected with human immunodeficiency virus type 1 . Two high-dose regimens , FPV 1,400 mg twice a day ( BID ) plus RTV 100 mg BID and FPV 1,400 mg BID plus RTV 200 mg BID , were planned to be compared to the approved regimen , FPV 700 mg BID plus RTV 100 mg BID , in a randomized three-period crossover study . Forty-two healthy adult subjects were enrolled , and 39 subjects completed period 1 . Due to marked hepatic transaminase elevations , predominantly with FPV 1,400 mg BID plus RTV 200 mg BID , the study was terminated prematurely . For FPV 1,400 mg BID plus RTV 100 mg BID , the values for plasma amprenavir ( APV ) area under the concentration-time profile over the dosing interval ( tau ) at steady state [ AUC ( 0-tau ) ] , maximum concentration of drug in plasma ( C ( max ) ) , and plasma concentration at the end of tau at steady state ( C ( tau ) ) were 54 , 81 , and 26 % higher , respectively , and the values for plasma RTV AUC ( 0-tau ) , C ( max ) , and C ( tau ) were 49 % higher , 71 % higher , and 11 % lower , respectively , than those for FPV 700 mg BID plus RTV 100 mg BID . For FPV 1,400 mg BID plus RTV 200 mg BID , the values for plasma APV AUC ( 0-tau ) , C ( max ) , and C ( tau ) were 26 , 48 , and 32 % higher , respectively , and the values for plasma RTV AUC ( 0-tau ) , C ( max ) , and C ( tau ) increased 4.15-fold , 4.17-fold , and 3.99-fold , respectively , compared to those for FPV 700 mg BID plus RTV 100 mg BID . FPV 1,400 mg BID plus RTV 200 mg BID is not recommended due to an increased rate of marked hepatic transaminase elevations and lack of pharmacokinetic advantage . FPV 1,400 mg BID plus RTV 100 mg BID is currently under clinical evaluation in multiple PI-experienced patients .
25496
Intervention_Pharmacological
fosamprenavir ( FPV )
25497
Intervention_Pharmacological
ritonavir ( RTV )
25498
Intervention_Pharmacological
FPV
25499
Intervention_Pharmacological
RTV
25500
Intervention_Pharmacological
FPV
25501
Intervention_Pharmacological
RTV
25502
Intervention_Pharmacological
FPV
25503
Intervention_Pharmacological
RTV
25504
Intervention_Pharmacological
FPV
25505
Intervention_Pharmacological
RTV
25506
Intervention_Pharmacological
FPV
25507
Intervention_Pharmacological
RTV
25508
Intervention_Pharmacological
FPV
25509
Intervention_Pharmacological
FPV
25510
Intervention_Pharmacological
FPV
25511
Intervention_Pharmacological
RTV
25512
Intervention_Pharmacological
FPV
25513
Intervention_Pharmacological
RTV
25514
Intervention_Pharmacological
FPV
25515
Intervention_Pharmacological
RTV
25516
Outcome_Physical
values for plasma amprenavir ( APV ) area
25517
Outcome_Physical
plasma concentration at the end of tau at steady state
25518
Outcome_Physical
values for plasma RTV AUC ( 0-tau )
25519
Outcome_Other
C ( max )
25520
Outcome_Other
C ( tau )
25521
Outcome_Physical
values for plasma APV AUC ( 0-tau )
25522
Outcome_Physical
plasma RTV AUC ( 0-tau )
25523
Outcome_Physical
C ( max )
25524
Outcome_Physical
C ( tau
25525
Outcome_Physical
rate of marked hepatic transaminase elevations
25526
Outcome_Other
lack of pharmacokinetic advantage .
25527
Participant_Condition
healthy
25528
Participant_Age
adult
25529
Participant_Sample-size
Forty-two
25530
Participant_Condition
healthy
25531
Participant_Age
adult