Pharmacokinetics and Safety of Fospropofol Disodium for Injection in Subjects with Hepatic Impairment Compared with Healthy Matched Controls: A Prospective Cohort Study

Fospropofol disodium is a water-soluble propofol prodrug used for procedural sedation and general anesthesia, but its pharmacokinetics in patients with impaired liver function had not been well characterized. This prospective cohort study compared fospropofol and its active metabolite propofol in patients with normal, moderate, or severe hepatic impairment against matched healthy controls following a single intravenous bolus, with concentrations measured by LC-MS/MS and pharmacokinetic parameters derived by non-compartmental analysis in Phoenix WinNonlin. Moderate hepatic impairment reduced fospropofol AUC by approximately 43% and increased its clearance by 60%, with a similar 55% AUC reduction in severe impairment, while clearance of the active metabolite propofol was reduced by 15-33% depending on severity – an inverse pattern of faster prodrug elimination alongside slower metabolite elimination. Preoperative albumin was identified as an independent predictor of fospropofol exposure, and no unexpected adverse events were observed after a single dose. This is the first study to characterize altered fospropofol pharmacokinetics in hepatic impairment, informing potential dose adjustment considerations for repeated dosing in this population.