Pharmacokinetics and safety of glecaprevir and pibrentasvir in HCV-negative subjects with hepatic impairment.
Purpose: This study characterized the effects of hepatic impairment on the pharmacokinetics and safety of glecaprevir and pibrentasvir, two direct-acting antivirals used for treatment of chronic HCV infection.Methods: HCV-negative subjects with normal hepatic function, or with mild (Child-Pugh [CP]-...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 75; no. 2; pp. 217 - 227 |
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| Autores principales: | , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
Feb2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=134311057&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 134311057 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Feb2019 vid: 75 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 134311057 134311057 134311057 10.1007/s00228-018-2576-4 134311057 ppf: 217 ppct: 10 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Pharmacokinetics and safety of glecaprevir and pibrentasvir in HCV-negative subjects with hepatic impairment. aug: au: Kosloski, Matthew P. Liu, Wei Wang, Haoyu Pugatch, David Mensa, Federico J. Gane, Edward Lawitz, Eric Marbury, Thomas C. Preston, Richard A. Kort, Jens affil: Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North Chicago, IL, USA sug: subj: Protease Inhibitors Pharmacokinetics Antiviral Agents Pharmacokinetics Hepatitis C Drug Therapy Liver Diseases Metabolism Protease Inhibitors Therapeutic Use Antiviral Agents Therapeutic Use Patient Safety Human Hepatitis C Diagnosis Severity of Illness Protease Inhibitors Administration and Dosage Antiviral Agents Administration and Dosage Biochemical Phenomena Drug Therapy, Combination Headache Chemically Induced Protease Inhibitors Adverse Effects Antiviral Agents Adverse Effects Protease Inhibitors Blood Antiviral Agents Blood ab: Purpose: This study characterized the effects of hepatic impairment on the pharmacokinetics and safety of glecaprevir and pibrentasvir, two direct-acting antivirals used for treatment of chronic HCV infection.Methods: HCV-negative subjects with normal hepatic function, or with mild (Child-Pugh [CP]-A), moderate (CP-B), or severe (CP-C) hepatic impairment received single doses of pibrentasvir 120 mg alone or with glecaprevir 200 mg or 300 mg (n = 6/functional group/dose). Plasma pharmacokinetics and protein binding were evaluated. Doses were separated by ≥ 14 days of washout.Results: For the approved combination of glecaprevir 300 mg with pibrentasvir 120 mg, glecaprevir AUC was increased by 33% (CP-A), to 2.0-fold (CP-B), and to 11-fold (CP-C) relative to normal subjects; pibrentasvir AUC was ≤ 26% different (CP-A or CP-B) and increased to 2.1-fold (CP-C). For glecaprevir 200 mg with pibrentasvir 120 mg, glecaprevir AUC was increased by 80% (CP-A) or to 2.8-fold (CP-B), while pibrentasvir AUC was unaffected in the same subjects (≤ 12% difference). Pibrentasvir 120 mg alone AUC increased 51% (CP-A), 31% (CP-B), and to 5.2-fold (CP-C). The unbound fraction of glecaprevir was higher in CP-C subjects than normal subjects and pibrentasvir protein binding was similar across groups. The most common adverse event was headache; no events were serious.Conclusion: This study supported evaluation of the glecaprevir 300 mg with pibrentasvir 120-mg combination in HCV-infected subjects with CP-A hepatic impairment without dose adjustment. Elevated glecaprevir and/or pibrentasvir exposures are expected in HCV-infected patients with CP-B or CP-C hepatic impairment. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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