icon_folder.gif   Conference Reports for NATAP  
  ICAAC 41st Interscience Conference on Antimicrobial Agents and Chemotherapy
Chicago, Illinois, December 16-19
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Kaletra and Amprenavir Interaction
  Impact of ABT 378/r (Kaletra) on the amprenavir (APV) plasma concentrations in HIV-experienced patients treated by the association APV-ABT 378/r
two reports are below
first report written by Scott Penzak, PharmD, NIH
Meynard et. al. reported an interesting interaction between lopinavir-ritonavir (LPV-RTV) and amprenavir (APV).9 Plasma Cmin concentrations were determined in consecutive patients receiving:
--LPV-RTV 400 mg-100 mg twice daily (n=11)
--APV 600 mg twice daily + RTV 100 mg twice daily (n=36)
--LPV-RTV 400 mg-100 mg twice daily + APV 600 mg twice daily (n=10)
--LPV-RTV 400 mg-100 mg twice daily + APV 750 mg twice daily (n=5)
All patients received concurrent NRTIs without NNRTI therapy. APV median Cmins were:
--1,755 ng/mL (607-3066): APV 600 mg twice daily + RTV 100 mg twice daily
--778 ng/mL (190-2037): LPV-RTV 400 mg-100 mg twice daily + APV 600 mg twice daily
--998 ng/mL (669-3066): LPV-RTV 400 mg-100 mg twice daily + APV 750 mg twice daily
Median lopinavir Cmins were:
--3326 ng/mL (1316-6698): LPV-RTV 400 mg-100 mg twice daily
--2226 ng/mL (518-8722): LPV-RTV 400 mg-100 mg twice daily + APV 600 mg twice daily
--1716 ng/mL (347-4810): LPV-RTV 400 mg-100 mg twice daily + APV 750 mg twice daily
LPV-RTV appeared to markedly reduce APV exposure (by approximately 50%) in this study (p < .001). Unfortunately, the wide interpatient variability in APV concentrations and the small number of patients studied mandate that results from this study be interpreted cautiously. Nonetheless, these results support the use of a 750 mg twice daily dose of APV when given along with LPV-RTV as recommended by the LPV-RTV product information (Abbott). Admin istering APV 750 mg twice daily (with LPV-RTV) is expected to approximate the systemic APV exposure achieved with conventional APV dosing (1200 mg twice daily). When LPV-RTV is given concurrently with APV, it is probably ­based on these data- not possible to achieve plasma APV concentrations comparable to those achieved with APV 600 mg twice daily plus RTV 100 mg twice daily. Also of note, is that fact that APV appeared to lower LPV-RTV concentrations; but again, interpatient variability in LPV concentrations was large. Future investigations assessing the interaction between LPV-RTV and APV are being conducted in crossover fashion in order to reduce the impact of interpatient variability (due to diet, concomitant drugs etc.) in the disposition of these agents. Nonetheless, results from this study have scientists speculating that lopinavir and amprenavir may induce the CYP3A4-mediated metabolism of each other; further study is necessary to confirm or refute such speculation.

APV + Kaletra: Is there an interaction here?
Written by Steve Piscatelli, PharmD, Tibotec-Virco
There has been much recent debate regarding the potential interaction between Kaletra (lopinavir/ritonavir) and APV. Data from the recent HIV Clinical Pharmacology meeting in Noordwijk, the Netherlands, earlier this year suggested that there may be a detrimental interaction between these three protease inhibitors.13 Investigators from France examined LPV and APV levels in four groups of patients. Kaletra alone (n=11), APV/RTV 600/100 mg (n=36), Kaletra + APV 600 mg (n=10), and Kaletra + APV 750 mg (n=5).14 Median trough concentrations of APV 600 mg were decreased from 1755 ng/ml when given with RTV alone to 778 ng/ml when given with Kaletra. Also, lopinavir troughs were decreased from 3326 ng/ml alone to 2226 ng/ml with 600 mg APV and 1716 ng/ml with 750 mg APV. These data are suggestive of a bi-directional drug interaction lowering both PIs, however this study has limitations in both its sample size and its design. A comparison of concentrations across different patient groups is limited by a number of factors including immunologic status, concomitant meds, diet, and demographics of the groups being compared. The previous study also compared different patient groups or compared the data from the combined Kaletra+ APV group to historical controls. These two studies raise the question that there may be some reduction in PI levels perhaps by induction of metabolism or other mechanisms. Two studies with cross-over designs are currently underway and may help to finally sort out this interesting interaction. From a clinical standpoint, the concentrations of both APV and LPV in this study were still adequate and well above the IC50 values, even for many resistant HIV strains. The poster abstract reported APV Cmin remained >500ng/ml in all patients except one; the impact of this interaction on the clinical efficacy of the combination remains to be seen.