Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2006 Abstracts

Abstract #A-367: Pharmacokinetic interaction between the protease inhibitor TMC114 and lopinavir/ritonavir
V.J. Sekar et al.

The purpose of this study was to evaluate the interaction between TMC114 with and without RTV and LPV/r in HIV infected subjects.

This study was conducted in two panels of 16 HIV infected subjects. One panel received LPV/r then had TMC114/r 1200/100 and 600/100 mg added sequentially. The other panel started with LPV/r then they were switched to TMC114 1200 mg plus LPV/r 533/133 mg and 600/100 mg sequentially. All drugs were given twice daily and PK studies were done on day 14 of treatment.

TMC114 did not affect LPV PK. The plasma concentrations of TMC114 were significantly decreased regardless of increased dosing or RTV coadministration. There was a 38% and 51% decrease in TMC AUC and Cmin due to LPV/r coadministration despite a 2 fold increase in dose.

The authors concluded that combination of TMC114 and LPV/r is not recommended due to a significant decrease in TMC exposure.

Abstract #A-368: Pharmacokinetic interaction between ethinyl estradiol, norethindrone and TMC114, a new protease inhibitor
V.J. Sekar et al.

The purpose of this study was to evaluate the interaction between TMC114 and estrogen containing contraceptives.

Eighteen healthy women received Ortho-Novum 1/35 for 21 days of two 28 day treatments. During the second treatment subjects received TMC 114/r 600/100 mg twice daily for 14 days with PK assessment on day 14 for both treatments.

TMC114/r significantly decreased the plasma concentrations of ethinyl estradiol. Ehinyl estradiol and norethindrone AUC decreased by 62% and 30%, respectively, when coadministered with TMC114/r.

The authors concluded that alternative or additional contraceptive methods would be necessary when TMC114/r is given with estrogen based contraceptives.

Abstract #A-369: Pharmacokinetic interaction between TMC114, a new protease inhibitor, and sildenafil
V.J. Sekar et al.

The purpose of this study was to evaluate the interaction between TMC114 and sildenafil.

Sixteen healthy subjects received one dose of sildenafil 100 mg then TMC114/r 400/100 mg twice daily for 8 days with a single 25 mg dose of sildenafil on day 7. 48 hour PK assessments were done after each dose of sildenafil.

TMC114/r significantly increased the plasma concentrations of sildenafil. Despite the 75% reduction in dose, sildenafil plasma concentrations (AUC) were similar when comparing the 100 mg to the 25 mg dose and there was significantly less sildenafil metabolite (95% decrease) when the lower dose was administered with TMC114/r.

The authors concluded that sildenafil dose reduction is necessary during TMC114/r coadministration and suggest avoiding doses higher than 25 mg.

Abstract #A-371: Pharmacokinetic evaluation of the interaction between TMC125 and tenofovir disoproxil fumarate
M. Scholler-Gyure et al.

The purpose of this study was to evaluate the interaction between TMC125 and tenofovir.

Twenty four healthy male subjects received TMC125 200 mg twice daily for 7 days with a single dose on day 8. Following a 14 day washout period subjects then received TDF 300 mg daily for 16 days during which they were randomized to receive TMC125 200 mg twice daily on days 9-15 or 1-7. The TMC125 AUC, Cmax and Cmin (90% CI) was 81% (75-88), 81% (75-88), 82% (73-91) during TDF coadministration, respectively. TDF AUC, Cmax and Cmin were 115% (109-121), 115% (104-127) and 119% (113-126), respectively, during TMC coadministration.

Although the plasma concentrations of TMC125 were lower, the authors concluded that it is unlikely that this decrease will translate into clinical significance and that the two drugs can be given together without dose adjustment.