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The Influence of Renal or Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Oliceridine
Oliceridine is a G protein–biased ligand at the μ‐opioid receptor in development for treatment of moderate to severe acute pain. A phase 1, open‐label, single‐dose study investigated the pharmacokinetics and safety of oliceridine 0.5 mg intravenous (IV) in subjects with end‐stage renal disease (ESRD...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383509/ https://www.ncbi.nlm.nih.gov/pubmed/31697049 http://dx.doi.org/10.1002/cpdd.750 |
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author | Nafziger, Anne N. Arscott, Kelly A. Cochrane, Kristina Skobieranda, Franck Burt, David A. Fossler, Michael J. |
author_facet | Nafziger, Anne N. Arscott, Kelly A. Cochrane, Kristina Skobieranda, Franck Burt, David A. Fossler, Michael J. |
author_sort | Nafziger, Anne N. |
collection | PubMed |
description | Oliceridine is a G protein–biased ligand at the μ‐opioid receptor in development for treatment of moderate to severe acute pain. A phase 1, open‐label, single‐dose study investigated the pharmacokinetics and safety of oliceridine 0.5 mg intravenous (IV) in subjects with end‐stage renal disease (ESRD, n = 9) versus 1 mg in healthy controls (n = 8). A second phase 1, open‐label, single‐dose study investigated the pharmacokinetics and safety of a 0.5‐mg IV dose in hepatic impairment (mild, n = 10; moderate, n = 10; severe, n = 6) versus 1 mg in healthy controls (n = 8). The controls were sex and age (±10 years) matched. In ESRD versus healthy subjects, no difference in clearance was observed between ESRD patients and subjects with normal renal function. Oliceridine clearance and AUC were not affected by hepatic impairment. Half‐life (hours; GM [%CV]) increased in subjects with moderate (4.3 [44.1]) and severe (5.8 [41.2]) impairment versus mild impairment (2.6 [20.0]) and healthy subjects (2.1 [11.3]). Volume of distribution was increased with the degree of hepatic impairment. All adverse events were mild and generally consistent with the known safety profile of oliceridine. No dose adjustment is needed in patients with renal impairment or in patients with mild or moderate hepatic impairment. Initial dose reduction should be considered in severe hepatic impairment, and patients may require fewer doses of oliceridine due to the longer half‐life observed in these patients. |
format | Online Article Text |
id | pubmed-7383509 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73835092020-07-27 The Influence of Renal or Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Oliceridine Nafziger, Anne N. Arscott, Kelly A. Cochrane, Kristina Skobieranda, Franck Burt, David A. Fossler, Michael J. Clin Pharmacol Drug Dev Articles Oliceridine is a G protein–biased ligand at the μ‐opioid receptor in development for treatment of moderate to severe acute pain. A phase 1, open‐label, single‐dose study investigated the pharmacokinetics and safety of oliceridine 0.5 mg intravenous (IV) in subjects with end‐stage renal disease (ESRD, n = 9) versus 1 mg in healthy controls (n = 8). A second phase 1, open‐label, single‐dose study investigated the pharmacokinetics and safety of a 0.5‐mg IV dose in hepatic impairment (mild, n = 10; moderate, n = 10; severe, n = 6) versus 1 mg in healthy controls (n = 8). The controls were sex and age (±10 years) matched. In ESRD versus healthy subjects, no difference in clearance was observed between ESRD patients and subjects with normal renal function. Oliceridine clearance and AUC were not affected by hepatic impairment. Half‐life (hours; GM [%CV]) increased in subjects with moderate (4.3 [44.1]) and severe (5.8 [41.2]) impairment versus mild impairment (2.6 [20.0]) and healthy subjects (2.1 [11.3]). Volume of distribution was increased with the degree of hepatic impairment. All adverse events were mild and generally consistent with the known safety profile of oliceridine. No dose adjustment is needed in patients with renal impairment or in patients with mild or moderate hepatic impairment. Initial dose reduction should be considered in severe hepatic impairment, and patients may require fewer doses of oliceridine due to the longer half‐life observed in these patients. John Wiley and Sons Inc. 2019-11-07 2020-07 /pmc/articles/PMC7383509/ /pubmed/31697049 http://dx.doi.org/10.1002/cpdd.750 Text en © 2019 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Articles Nafziger, Anne N. Arscott, Kelly A. Cochrane, Kristina Skobieranda, Franck Burt, David A. Fossler, Michael J. The Influence of Renal or Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Oliceridine |
title | The Influence of Renal or Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Oliceridine |
title_full | The Influence of Renal or Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Oliceridine |
title_fullStr | The Influence of Renal or Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Oliceridine |
title_full_unstemmed | The Influence of Renal or Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Oliceridine |
title_short | The Influence of Renal or Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Oliceridine |
title_sort | influence of renal or hepatic impairment on the pharmacokinetics, safety, and tolerability of oliceridine |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383509/ https://www.ncbi.nlm.nih.gov/pubmed/31697049 http://dx.doi.org/10.1002/cpdd.750 |
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