1101 the Effect of Renal Impairment and End Stage Renal Disease on the Single-Dose Pharmacokinetics of Psi-7977

Cornpropst, Melanie; Denning, Jeannette; Clemons, David; Marbury, T.; Alcorn, Harry; Smith, William B.; Sale, Michèle M.; Fang, Liang; Berrey, M. Michelle; Symonds, William T.

doi:10.1016/s0168-8278(12)61113-1

Cited by 67 publications

(59 citation statements)

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“…Data have started emerging regarding the use of SOF in patients with CKD/ESRD. 149 Even though HCV-TARGET real-life data on use of combination of various DAAs including SOF in various stages of CKD including patients with ESRD showed high SVR12 response rates, it was associated with higher side effects including worsening of renal functions in a quarter of the patients. 150 However, two recent studies that used combination of SOF (half dose or full dose) in combination with full dose of simeprevir have shown SOF to be safe with very high efficacy (SVR 12-99-100%) in patients with ESRD.…”

Section: Absence Of Untreatable Diseasesmentioning

confidence: 99%

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Puri

Saraswat

Dhiman

et al. 2016

Journal of Clinical and Experimental Hepatology

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India contributes significantly to the global burden of HCV. While the nucleoside NS5B inhibitor sofosbuvir became available in the Indian market in March 2015, the other directly acting agents (DAAs), Ledipasvir and Daclatasvir, have only recently become available in the India. The introduction of these DAA in India at a relatively affordable price has led to great optimism about prospects of cure for these patients as not only will they provide higher efficacy, but combination DAAs as all-oral regimen will result in lower side effects than were seen with pegylated interferon alfa and ribavirin therapy. Availability of these newer DAAs has necessitated revision of INASL guidelines for the treatment of HCV published in 2015. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. The availability of combination DAA therapy has simplified therapy of HCV with decreased reliance of evaluation for monitoring viral kinetics or drug related side effects. ( J CLIN EXP HEPATOL 2016;6:119-145) T here have been revolutionary changes in the management of chronic hepatitis C (CH-C) over the last few years. Pegylated interferon alfa (Peg-IFNa) plus ribavirin (RBV) therapy, which till the recent past was the standard of care, has been eclipsed by the arrival of newer directly acting antiviral agents (DAAs). Not only do the DAAs have better efficacy, they are also associated with lower side effects, have better tolerability, a shorter duration of therapy, and have simpler administration.In the recent guidelines issued by the American Association for the study of Liver Diseases (AASLD), in collaboration with the Infectious Diseases Society of America 1 and the European Association for Study of the Liver z (EASL), 2 the role of Peg-IFNa/RBV therapy in the management of HCV has been relegated to second-line, backup status. These newer guidelines, however, cannot be implemented in India as many of the recommended drugs are yet to be marketed in India. Other considerations for the treatment of HCV in India are a predominance of

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Section: Absence Of Untreatable Diseasesmentioning

confidence: 99%

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Puri

Saraswat

Dhiman

et al. 2016

Journal of Clinical and Experimental Hepatology

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“…Accordingly, clinically significant changes in GS-331007 pharmacokinetics were noted in the renal impairment (RI) study (Sect. 3.7.2) [8]. GS-331007 CL R was *2.0-fold higher than glomerular filtration rate (GFR), suggesting contribution of active secretion to GS-331007 CL R .…”

Section: Metabolism and Eliminationmentioning

confidence: 94%

Pharmacokinetic, Pharmacodynamic, and Drug-Interaction Profile of the Hepatitis C Virus NS5B Polymerase Inhibitor Sofosbuvir

et al. 2015

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Sofosbuvir (SOVALDI(®)), a potent, once-daily, orally administered nucleotide analog prodrug inhibitor of the hepatitis C virus (HCV) NS5B polymerase is approved in the USA, EU, Canada, and other regions for the treatment of HCV infection as a component of an antiviral treatment regimen. Sofosbuvir undergoes intracellular activation to form GS-461203 (active triphosphate, not detected in plasma), and ultimately the inactive, renally eliminated metabolite GS-331007. GS-331007 was identified as the primary analyte of interest for clinical pharmacology studies as it accounted for >90 % of systemic drug-related material exposure, and provided comparable exposure-response relationships for viral kinetics as observed for sofosbuvir. GS-331007 and sofosbuvir exhibit linear pharmacokinetics with minimal accumulation upon multiple dosing. Compared to healthy subjects, HCV-infected patients had modestly lower (39 %) GS-331007 area under the plasma concentration-time curve (AUC) and higher sofosbuvir AUC (60 %). Sofosbuvir can be administered without dose modification in HCV-infected patients with any degree of hepatic impairment or mild to moderate renal impairment. Sofosbuvir has a low propensity for clinically significant drug interactions with common concomitant medications used by HCV-infected patients. Clinically significant alterations in GS-331007 or sofosbuvir exposures are limited to potent inducers of intestinal P-glycoprotein that may lower exposure. In HCV-infected patients, demographic variables do not significantly influence GS-331007 and sofosbuvir exposures and no consistent exposure-response relationships were observed for efficacy or safety. This review focuses on the clinical pharmacokinetics, pharmacodynamics, and pharmacokinetic-pharmacodynamic relationships of sofosbuvir, and summarizes a number of drug interaction studies with important concomitant medications commonly used by HCV-infected patients.

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“…Sofosbuvir, a prodrug efficiently extracted by first-pass hepatic uptake, avoids significant renal excretion. In the liver, sofosbuvir is metabolized to the uridine monophosphate that can either be further phosphorylated to the active triphosphate form (GS-461203), a uridine triphosphate analog that functions as a defective substrate of the HCV nonstructural (NS)5B polymerase and thus inhibits HCV RNA synthesis [3], or dephosphorylated to the free nucleoside. The free nucleoside enters the circulation and is excreted primarily in the urine.…”

Section: Discussionmentioning

confidence: 99%

A New Standard of Care? Standard Dose Sofosbuvir in an HCV-Infected Liver Transplant Recipient Undergoing Hemodialysis

et al. 2015

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1101 the Effect of Renal Impairment and End Stage Renal Disease on the Single-Dose Pharmacokinetics of Psi-7977

Cited by 67 publications

References 0 publications

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Pharmacokinetic, Pharmacodynamic, and Drug-Interaction Profile of the Hepatitis C Virus NS5B Polymerase Inhibitor Sofosbuvir

A New Standard of Care? Standard Dose Sofosbuvir in an HCV-Infected Liver Transplant Recipient Undergoing Hemodialysis

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