Coadministration with lopinavir and ritonavir decreases exposure to BILR 355, a nonnucleoside reverse transcriptase inhibitor, in healthy volunteers.
The objective of this investigation was to evaluate the pharmacokinetic interaction of lopinavir/ritonavir (LPV/r) with BILR 355. In group A, 26 healthy participants were administered LPV/r (400mg/100mg) twice daily for 14 days, followed by coadministration of BILR 355, 150 mg twice daily for an additional 7 days. Pharmacokinetic assessments were performed on days 14 and 21. In group B, 8 healthy participants were given BILR 355/ritonavir (BILR 355/r, 150 mg/100mg) twice daily for 7 days. The pharmacokinetic data from group B (BILR 355/r-alone group) were also pooled with group B subjects from 3 similar phase I drug-drug interaction trials performed in parallel to this study. Coadministration with LPV/r resulted in a 51% decrease in steady-state area under plasma concentration-time curve from 0 to 12 hours (AUC(0-12,ss)) and steady-state maximum measured plasma concentration over a dosing interval (C(max,ss)) and a 50% decrease in steady-state plasma concentration 12 hours post last dosing (C(12,ss)) for BILR 355. Exposure to LPV was not changed after coadministration. BILR 355/r was well tolerated in this study. There was no evidence of increased risk of lopinavir or ritonavir toxicity upon coadministration with BILR 355.
Huang
Fenglei
F
Clinical Pharmacokinetics & Pharmacodynamics, Boehringer Ingelheim Pharmaceuticals, Inc, 900 Ridgebury Rd, Ridgefield, CT 06877-0368, USA. fenglei.huang@boehringer-ingelheim.com
Scholl
Paul
P
Huang
David B
DB
MacGregor
Thomas R
TR
Vinisko
Richard
R
Castles
Mark A
MA
Berger
Frank
F
Robinson
Patrick
P
D000328:Adult; D001381:Azepines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
C548654:5,11-dihydro-11-ethyl-5-methyl-8-(2-(1-oxido-4-quinolinyl)ethyl)-6H-dipyrido(3,2-B,2',3'-E)(1,4)diazepin-6-one; D001381:Azepines; D017320:HIV Protease Inhibitors; D011725:Pyridines; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D019438:Ritonavir