The Influence of Renal or Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Oliceridine
| Autor: | Michael J. Fossler, Kelly A. Arscott, David A. Burt, Franck Skobieranda, Kristina Cochrane, Anne N. Nafziger |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male renal impairment medicine.medical_specialty hepatic impairment Oliceridine Receptors Opioid mu Pharmaceutical Science Original Manuscript Thiophenes Ligands 030226 pharmacology & pharmacy Gastroenterology Severity of Illness Index oliceridine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Internal medicine Medicine Humans Pharmacology (medical) In patient Spiro Compounds Adverse effect Volume of distribution business.industry Hepatic impairment Liver Diseases G protein–biased ligand Articles Middle Aged Acute Pain Healthy Volunteers Safety profile chemistry Tolerability 030220 oncology & carcinogenesis Case-Control Studies Kidney Failure Chronic Administration Intravenous Female Safety business pharmacokinetics Half-Life |
| Zdroj: | Clinical Pharmacology in Drug Development |
| ISSN: | 2160-7648 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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