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Mutation Information
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Mutation Site
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Y181C |
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Mutation Type
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Amino acid level |
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Gene/Protein/Region Type
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RT |
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Combined Mutation
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rt.Y181C+rt.K103N |
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Relevant Drug
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doravirine (DOR) |
Literature Information
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PubMed PMID
|
32816220
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Published Year
|
2020 |
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Journal
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Clinical drug investigation |
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Title
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Clinical Pharmacokinetics of the Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor Doravirine: An Assessment of the Effect of Patient Characteristics and Drug-Drug Interactions. |
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Author
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Khalilieh S,Yee KL,Sanchez R,Stoch SA,Wenning L,Iwamoto M |
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Evidence
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Even at this decreased C24, doravirine plasma concentrations exceed the pharmacokinetic target of 78 nM, which is greater than 6-fold the in vitro IC50 for inhibition of wild-type virus, and exceeds IC50 values for common single resistance mutations (K103N, Y181C, G190A), and of the K103N/Y181C double mutant. Steady-state AUC was selected as the exposure measure from which to judge clinical relevance from a safety perspective, as this parameter is an integration of concentrations over the 24-h dosing interval in which individuals are exposed to doravirine at steady state.
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HIV Mutation Detail Information