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Published byEustacia Holland Modified over 6 years ago
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Pharmacokinetics and Drug Interactions in the new HCV Clinical Management SOC
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Why worry about Pharmacokinetics (PK) and Drug – Drug Interactions (DDIs) in managing HCV patients?
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Interaction due to Enzyme Inhibition: Increased systemic exposure
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Interaction due to Enzyme Induction: Decreased systemic exposure
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The importance of Cytochrome P450 (CYP) enzymes
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Drugs can be metabolised in the Gastrointestinal tract and Liver
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Drugs can be transported in the Gastrointestinal tract and Liver
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Understanding the disposition of the DAAs
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Telaprevir DDIs
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Telaprevir increases exposure to CYP3A substrates: Perpetrator
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Telaprevir increases exposure to CYP3A substrates
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Telaprevir decreases exposure to other CYP substrates
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Telaprevir decreases total but not unbound methadone concentrations.
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Enzyme inducing agents reduce telaprevir exposure: Victim
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Interactions with Boosted PIs
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Telaprevir: DDIs with HIV antiretrovirals
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Key CROI abstract
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Boceprevir DDIs
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Boceprevir increases exposure to CYP3A substrates
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Boceprevir decreases exposure to other CYP substrates
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Boceprevir exposure is decreased by efavirenz
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Interaction of Boceprevir and Boosted HIV PIs
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Boceprevir does not alter the PK of Raltegravir
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Key CROI abstract
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DAA Clinical Pharmacology
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Contraindications with telaprevir and boceprevir
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Drug Survey: Outline
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Management of Drug-Drug Interactions
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Disposition of Antidepressants
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DAAs and Lipid Lowering Agents
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Implications for clinical practice
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TMC435 (Simeprivir)
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TMC435 (Simeprivir) Interactions
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BMS
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DAA clinical pharmacology: conclusions
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Thank you
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