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Pharmacokinetic interaction between etravirine and lopinavir/ritonavir
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Reported by Jules Levin
ICAAC Sept 11-15 2009 San Francisco
Monika Scholler-Gyure,1 Thomas N Kakuda,2 Sophie H Akuma,1 Inge De Clerq,1 Goedele De Smedt,1 Kurt Spittaels,1 Katrien Janssen,1 Veerle Vyncke,1 Richard MW Hoetelmans1
1Tibotec BVBA, Mechelen, Belgium; 2Tibotec Inc., Yardley, PA, USA
AUTHOR CONCLUSIONS
ETR had no clinically relevant effect on the pharmacokinetics of LPV and RTV
When co-administered with the Meltrex formulation of LPV/r, ETR PK parameters decreased by 30-45%
The effect of the Meltrex formulation of LPV/r on ETR is comparable to that seen with DRV/r7
- efficacy and safety of ETR in the presence of DRV/r was demonstrated in DUET-1 and DUET-24
Co-administration of ETR and LPV/r was generally safe and well tolerated
ETR can be co-administered with LPV/r without dose adjustments
ABSTRACT
Background
Etravirine (ETR; TMC125) is a next-generation NNRTI with demonstrated activity in treatment-experienced, HIV-1-infected patients. A previous interaction trial in HIV-negative volunteers demonstrated increased ETR exposure when co administered with lopinavir/ritonavir (LPV/r; RTV) (soft-gel formulation). This study re-evaluated the pharmacokinetics of ETR and LPV/r when LPV/r was administered as the Meltrex formulation.
Methods
Open-label, randomized, two-way, two-period crossover trial. ETR 200mg bid was given for 8 days. After 14 days washout, LPV/r 400/100mg bid was administered for 16 days; ETR 200mg bid was co-administered on Days 9-16. Steady-state pharmacokinetics were assessed over 12 hours for ETR, LPV and RTV alone and when co-administered. Pharmacokinetic (PK) parameters were obtained by non-compartmental analysis. Safety and tolerability were assessed.
Results
Sixteen volunteers participated (11 male/five female). PK results are given below (Table 1).
Table 1. Mean (± SD) PK parameters for ETR and LPV alone and co-administered
RTV pharmacokinetics were unchanged. The most frequent adverse event (AE) was headache in six volunteers (grade 1). One grade 3 increase of triglycerides was reported during co-administration.
Conclusions
In contrast to the results of the study performed with the soft-gel LPV/r, co-administration of ETR with LPV/r (Meltrex) resulted in a 30-45% decrease in ETR pharmacokinetics. The decrease of LPV PK parameters by 13-20% when combined with ETR is similar to earlier reported data and is not considered clinically relevant. Given that the effect of LPV/r on ETR pharmacokinetics is comparable to the effect of darunavir/ritonavir (DRV/r) on ETR pharmacokinetics shown in previous trials, which demonstrated favorable ETR efficacy and safety, ETR and LPV/r can be co-administered without dose adjustments.
REFERENCES
1. Vingerhoets J, et al. J Virol 2005;79:12773-82.
2. Madruga JV, et al. Lancet 2007;370:29-38.
3. Lazzarin A, et al. Lancet 2007;370:39-48.
4. Mills A, et al. IAS 2009. Abstract MOPEB036.
5. Yeh RF, et al. JAIDS 2006;42:52-60.
6. Piscitelli S, et al. ICAAC 2002. Abstract A-1824.
7. Scholler-Gyure M, et al. Antiviral Ther 2007;12:789-96.
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