Disposition of Oral Nalbuphine and Its Metabolites in Healthy Subjects and Subjects with Hepatic Impairment: Preliminary Modeling Results Using a Continuous Intestinal Absorption Model with Enterohepatic Recirculation

• Published in: Metabolites Vol. 14; no. 9; p. 471
• Main Authors: Nagar, Swati, Hawi, Amale, Sciascia, Thomas, Korzekwa, Ken
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.09.2024; MDPI
• Subjects: Analgesics; Bioavailability; Comparative analysis; Differential equations; Drug dosages; Drug interaction; drug metabolism; enterohepatic recycling; Enzymes; hepatic impairment; Intestinal absorption; Intestine; Isoenzymes; Liver; mechanistic modeling; Metabolism; Metabolites; Nalbuphine; Oral administration; Partial differential equations; Pharmacokinetics; Physiological aspects; Plasma; Proteins; United States > US; hepatic impairment; pharmacokinetics; enterohepatic recycling; nalbuphine; mechanistic modeling; drug metabolism

Nalbuphine (NAL) is a mixed κ-agonist/μ-antagonist opioid with extensive first-pass metabolism. A phase 1 open-label study was conducted to characterize the pharmacokinetics (PKs) of NAL and select metabolites following single oral doses of NAL extended-release tablets in subjects with mild, moderat...