Pharmacokinetic interactions between telaprevir and antiretroviral drugs in HIV/HCV-coinfected patients with advanced liver fibrosis and prior HCV non-responders

Milazzo, Laura; Cattaneo, Dario; Calvi, Elisa; Gervasoni, Cristina; Mazzali, Cristina; Ronzi, Paola; Peri, Anna Maria; Ridolfo, Anna Lisa; D’Avolio, Antonio; Antinori, Spinello

doi:10.1016/j.ijantimicag.2014.12.035

Cited by 6 publications

(1 citation statement)

References 16 publications

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“…This interaction limits the administration of telaprevir in combination with RBV in patients presenting several comorbidities, such as renal impairment. Considering this high drug--drug interaction profile, there is a key population, because the high HCV prevalence and the use of concomitant medication, in which telaprevir is especially sensitive (such, HIV co-infected patients), due to telaprevir presents drug--drug interactions, requiring drug dose modification, with all the HIV protease inhibitor [61]. Third, telaprevir antiviral activity is weaker in patients with HCV-genotype 2 or 4, and there is a complete loss of effectiveness when is administered to patients infected with genotype 3.…”

Section: Expert Opinionmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic evaluation of telaprevir for the treatment of hepatitis C

Rivero‐Juárez

Camacho²,

Rivero³

2015

Expert Opinion on Drug Metabolism & Toxicology

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Section: Expert Opinionmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic evaluation of telaprevir for the treatment of hepatitis C

Rivero‐Juárez

Camacho²,

Rivero³

2015

Expert Opinion on Drug Metabolism & Toxicology

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Effect of hepatitis B and C clearance on atazanavir exposure

Gervasoni

Cattaneo

Micheli

et al. 2015

Eur J Clin Pharmacol

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Designing Out PXR Activity on Drug Discovery Projects: A Review of Structure-Based Methods, Empirical and Computational Approaches

Hall

Chanteux

Ménochet³

et al. 2021

J. Med. Chem.

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This perspective discusses the role of pregnane xenobiotic receptor (PXR) in drug discovery and the impact of its activation on CYP3A4 induction. The use of structural biology to reduce PXR activity on drug discovery projects has become more common in recent years. Analysis of this work highlights several important molecular interactions, and the resultant structural modifications to reduce PXR activity are summarized. The computational approaches undertaken to support the design of new drugs devoid of PXR activation potential are also discussed. Finally, the SAR of empirical design strategies to reduce PXR activity is reviewed, and the key SAR transformations are discussed and summarized. In conclusion, this perspective demonstrates that PXR activity can be greatly diminished or negated on active drug discovery projects with the knowledge now available. This perspective should be useful to anyone who seeks to reduce PXR activity on a drug discovery project.

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Pharmacokinetic interactions between telaprevir and antiretroviral drugs in HIV/HCV-coinfected patients with advanced liver fibrosis and prior HCV non-responders

Cited by 6 publications

References 16 publications

Pharmacokinetic and pharmacodynamic evaluation of telaprevir for the treatment of hepatitis C

Pharmacokinetic and pharmacodynamic evaluation of telaprevir for the treatment of hepatitis C

Effect of hepatitis B and C clearance on atazanavir exposure

Designing Out PXR Activity on Drug Discovery Projects: A Review of Structure-Based Methods, Empirical and Computational Approaches

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