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.

ABCB11 and ABCB1 gene polymorphisms impact on telaprevir pharmacokinetic at one month of therapy

CUSATO, JESSICA
First
;
ALLEGRA, SARAH;DE NICOLO', AMEDEO;BOGLIONE, Lucio;FATIGUSO, GIOVANNA;CIANCIO, Alessia;SMEDILE, Antonina;STRONA, Silvia;RIZZETTO, Mario;DI PERRI, Giovanni;D'AVOLIO, ANTONIO
Last
2015

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.
69
1 February 2015
63
69
Cusato, Jessica; Allegra, Sarah; DE NICOLO', Amedeo; Boglione, Lucio; Fatiguso, Giovanna; Giuseppe, Cariti; Ciancio, Alessia; Smedile, Antonina; Strona, Silvia; Giulia, Troshina; Rizzetto, Mario; DI PERRI, Giovanni; D'Avolio, Antonio
File in questo prodotto:
File Dimensione Formato  
30 ABCB11 and ABCB1 gene polymorphisms impact on telaprevir.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 750.99 kB
Formato Adobe PDF
750.99 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/151945
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 11
social impact