title: ABCB11 and ABCB1 gene polymorphisms impact on telaprevir pharmacokinetic at one month of therapy.
abstract: In 2011 direct-acting antivirals, including telaprevir, have been developed to achieve a better antiviral effect. It was reported that telaprevir is a substrate of P-glycoprotein (ABCB1) and cytochrome P450 3A4. The aim of this retrospective study was the evaluation of the influence of some single nucleotide polymorphisms (SNPs) of genes (ABCB1, SLC28A2/3, SLC29A1) involved in TLV and RBV transport and their correlation with plasma TLV drug exposure at 1 month of therapy. We also investigated the association of a SNP in ABCB11 gene, whose role in TLV transport was not yet shown. Twenty-nine HCV-1 patients treated with telaprevir, ribavirin and pegylated-interferon-α were retrospectively analyzed; allelic discrimination was performed by real-time PCR. Telaprevir Ctrough levels were influenced by Metavir score (P=0.023), ABCB1 2677 G>T (P=0.006), ABCB1 1236 C>T (P=0.015) and ABCB11 1131 T>C (P=0.033) SNPs. Regarding ABCB1 3435 C>T, a not statistically significant trend in telaprevir plasma concentration was observed. Metavir score (P=0.002, OR -336; 95% CI -535;-138), ABCB1 2677 (P=0.020, OR 497; 95% CI 86; 910), ABCB11 1131 (P=0.002, OR 641; 95% CI 259;1023) and CNT2 -146 (P=0.006, OR -426; 95% CI -721;-132) were able to predict telaprevir plasma levels in the regression analysis. Other SNPs showed no association. This study reveals BSEP implication in telaprevir transport and confirms the involvement and influence of P-glycoprotein on telaprevir plasma levels. To date, no similar data concerning pharmacogenetics and pharmacokinetics were published, but further studies in different and bigger cohorts are needed.
authors: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy. Electronic address: jessica.cusato@yahoo.it.
authors: Jessica
authors: J
authors: Cusato
authors: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors: Sarah
authors: S
authors: Allegra
authors: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors: Amedeo
authors: A
authors: De Nicolò
authors: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors: Lucio
authors: L
authors: Boglione
authors: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors: Giovanna
authors: G
authors: Fatiguso
authors: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors: Giuseppe
authors: G
authors: Cariti
authors: Unit of Gastroenterology, University of Turin, Department of Medical Sciences, S. Giovanni Battista (Molinette) Hospital, Turin, Italy.
authors: Alessia
authors: A
authors: Ciancio
authors: Unit of Gastroenterology, University of Turin, Department of Medical Sciences, S. Giovanni Battista (Molinette) Hospital, Turin, Italy.
authors: Antonina
authors: A
authors: Smedile
authors: Unit of Gastroenterology, University of Turin, Department of Medical Sciences, S. Giovanni Battista (Molinette) Hospital, Turin, Italy.
authors: Silvia
authors: S
authors: Strona
authors: Unit of Gastroenterology, University of Turin, Department of Medical Sciences, S. Giovanni Battista (Molinette) Hospital, Turin, Italy.
authors: Giulia
authors: G
authors: Troshina
authors: Unit of Gastroenterology, University of Turin, Department of Medical Sciences, S. Giovanni Battista (Molinette) Hospital, Turin, Italy.
authors: Mario
authors: M
authors: Rizzetto
authors: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors: Giovanni
authors: G
authors: Di Perri
authors: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors: Antonio
authors: A
authors: D'Avolio
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D003710:Demography; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D016014:Linear Models; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009842:Oligopeptides / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C513055:ABCB1 protein, human; C093491:ABCB11 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D009842:Oligopeptides; C486464:telaprevir
keywords: Bile salt export pump; P-glycoprotein; Pharmacogenetics