Pharmacokinetics of elbasvir and grazoprevir in subjects with end-stage renal disease or severe renal impairment.
Purpose: To describe the phase 1 and population pharmacokinetic investigations that support dosing recommendations for elbasvir/grazoprevir (EBR/GZR) in hepatitis C virus-infected people with advanced chronic kidney disease. Methods: This was an open-label, two-part, multiple-dose trial (MK-5172 PN0...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 75; no. 5; pp. 665 - 676 |
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| Autores principales: | , , , , , , , , , , , |
| Formato: | clinical trial research tables/charts Journal Article |
| Publicado: |
Springer Nature
May2019
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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=135892073&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 135892073 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: May2019 vid: 75 iid: 5 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 135892073 135892073 135892073 10.1007/s00228-018-2585-3 135892073 ppf: 665 ppct: 11 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Pharmacokinetics of elbasvir and grazoprevir in subjects with end-stage renal disease or severe renal impairment. aug: au: Caro, Luzelena Wenning, Larissa Feng, Hwa-Ping Guo, Zifang Du, Lihong Bhagunde, Pratik Fandozzi, Christine Panebianco, Deborah Marshall, William L. Butterton, Joan R. Iwamoto, Marian Yeh, Wendy W. affil: Merck & Co., Inc., Kenilworth, NJ, USA sug: subj: Drug Evaluation Antiviral Agents Pharmacokinetics Antiviral Agents Administration and Dosage Hepatitis C Drug Therapy Kidney Failure, Chronic Therapy Severity of Illness Human Clinical Trials Kidney Diseases Drug Therapy Antiviral Agents Therapeutic Use Hemodialysis Confidence Intervals ab: Purpose: To describe the phase 1 and population pharmacokinetic investigations that support dosing recommendations for elbasvir/grazoprevir (EBR/GZR) in hepatitis C virus-infected people with advanced chronic kidney disease. Methods: This was an open-label, two-part, multiple-dose trial (MK-5172 PN050; NCT01937975) in 24 non–HCV-infected participants with end-stage renal disease (ESRD) or severe renal impairment who received once-daily EBR 50 mg and GZR 100 mg for 10 days. Population pharmacokinetic analyses from the phase 3 C-SURFER study (PN052, NCT02092350) were also conducted. Results: When comparing haemodialysis (HD) and non-HD days in participants with ESRD, geometric mean ratios (GMRs) (90% confidence intervals [CIs]) for EBR and GZR AUC0–24 were 1.14 (1.08–1.21) and 0.97 (0.87–1.09). When comparing ESRD and healthy participants, GMRs (90% CIs) for EBR and GZR AUC0–24 were 0.99 (0.75–1.30) and 0.83 (0.56–1.22) on HD days, and 0.86 (0.65–1.14) and 0.85 (0.58–1.25) on non-HD days. GMRs (90% CIs) for AUC0–24 in participants with severe renal impairment relative to healthy controls were 1.65 (1.09–2.49) for GZR and 1.86 (1.38–2.51) for EBR. In population modelling of data from C-SURFER, absolute geometric means of steady-state EBR AUC0–24 were 2.78 and 3.07 μM*h (HD and non-HD recipients) and GZR AUC0–24 were 1.80 and 2.34 μM*h (HD and non-HD recipients). Conclusions: EBR/GZR represents an important treatment option for HCV infection in people with severe renal impairment and those with ESRD. No dosage adjustment of EBR/GZR is required in people with any degree of renal impairment, including those receiving dialysis. pubtype: Academic Journal doctype: clinical trial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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