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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Lopinavir concentrations in cerebrospinal fluid exceed the 50% inhibitory concentration for HIV.

INTRODUCTION: Lopinavir (LPV) is highly bound to plasma proteins and is a substrate for active drugs transporters, which may greatly limit the access of LPV to the central nervous system (CNS). However, even low lopinavir concentrations may be sufficient to inhibit HIV replication. Prior anecdotal reports indicated that lopinavir concentrations were below detection in cerebrospinal fluid (CSF). METHODS: LPV was measured by liquid chromatography/ mass spectrometry in 31 CSF-plasma pairs from 26 HIV-infected individuals who were taking LPV-containing antiretroviral regimens. The lower limit of quantification was 3.7 microg/l. RESULTS: Seven of the sample pairs had very low plasma (and CSF) LPV concentrations, with a mean estimated plasma trough of 274 microg/l (range, < 3.7 to 608; typical trough values approximately 4000 microg/l), suggesting poor recent adherence. In the remaining 24 sample pairs, the median LPV concentration was 5889 microg/l [interquartile range (IQR), 4805-9620] and all CSF samples had measurable LPV concentrations: median 17.0 microg/l (IQR, 12.1-22.7). The median CSF-plasma ratio was 0.23% (range, 0.12-0.75). All CSF concentrations in these samples were more than double the 50% inhibitory concentration for wild-type HIV virus. CONCLUSIONS: In patients with typical plasma levels of LPV, the drug is detectable in the CSF at concentrations that exceed those needed to inhibit HIV replication. Despite being > 98% bound to plasma proteins, LPV penetrates into the CNS and may contribute to the control of HIV in this potential reservoir.[1]


  1. Lopinavir concentrations in cerebrospinal fluid exceed the 50% inhibitory concentration for HIV. Capparelli, E.V., Holland, D., Okamoto, C., Gragg, B., Durelle, J., Marquie-Beck, J., van den Brande, G., Ellis, R., Letendre, S. AIDS (2005) [Pubmed]
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