title: Lack of drug interaction between cyclosporine and telaprevir in a liver transplant recipient.
abstract: Telaprevir is a novel NS3A/4A protease inhibitor approved in combination with ribavirin and peg-interferon alfa for the treatment of genotype-1 chronic hepatitis C. This drug is also known to be a potent cytochrome P450 3A and drug efflux protein ATP-binding cassette B1 (also called P-glycoprotein) inhibitor, and could therefore interact with immunosuppressive drugs. For this reason, a decrease in cyclosporine (CsA) dosage has been proposed when combining this drug with telaprevir. We report herein the case of an unpredictable lack of interaction between CsA and telaprevir in a liver transplant recipient. The decrease in CsA dosage, conducted as recommended in the literature, did not result in stable CsA concentrations but decreased them. However, the decrease in CsA exposure could have been unseen without the measurement of CsA concentrations 2 h after the administration (C2 ) of the drug, because it mainly resulted from the decrease in CsA peak. The mechanism leading to this lack of drug interaction in this patient has not been fully elucidated yet, but is likely to affect the absorption phase. Therapeutic drug monitoring using only CsA trough concentrations could be falsely reassuring, and the addition of the measurement of the C2 may add useful information to adapt CsA dosage in patients co-treated with telaprevir.
authors.affiliation: Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital, Rennes, France; Laboratory of Experimental and Clinical Pharmacology, Faculty of Medicine, Rennes 1 University, Rennes, France; CIC-P 1414 Clinical Investigation Center, Inserm, Rennes, France; Faculty of Pharmacy, EA4123 Barrières physiologiques et réponses thérapeutiques, Paris XI University, Châtenay-Malabry, France.
authors.forename: F
authors.initials: F
authors.lastname: Lemaitre
authors.forename: C
authors.initials: C
authors.lastname: Jezequel
authors.forename: M-C
authors.initials: MC
authors.lastname: Verdier
authors.forename: M
authors.initials: M
authors.lastname: Dermu
authors.forename: C
authors.initials: C
authors.lastname: Boglione-Kerrien
authors.forename: K
authors.initials: K
authors.lastname: Boudjema
authors.forename: E
authors.initials: E
authors.lastname: Bellissant
mesh_terms: D016572:Cyclosporine / Q000493:pharmacokinetics*; D004347:Drug Interactions; D016903:Drug Monitoring; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016898:Interferon-alpha / Q000627:therapeutic use; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000493:pharmacokinetics*; D015842:Serine Proteinase Inhibitors / Q000493:pharmacokinetics*; D066027:Transplant Recipients
chemical_list: D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; C486464:telaprevir; D016572:Cyclosporine
keywords: antivirals; cyclosporine; hepatitis C virus; immunosuppressive drugs; liver transplant; pharmacokinetics; telaprevir; therapeutic drug monitoring