Fospropofol disodium for injection (FospropofolFP) is a recently introduced, water-soluble precursor of propofol used for procedural sedation and induction of anesthesia. This prospective cohort investigation assessed how hepatic dysfunction affects the pharmacokinetics and safety of FospropofolFP during general anesthesia, comparing impaired subjects with matched healthy individuals. A total of 23 participants were recruited and grouped by liver status: normal hepatic function (n = 10), moderate impairment (n = 10), and severe impairment (n = 3). Each person received FospropofolFP 10 mg/kg i.v. as a single bolus. Fourteen venous samples per subject were obtained. Concentrations of FospropofolFP and its released metabolite, propofol, were quantified via LC-MS/MS. Noncompartmental analysis (NCA) using Phoenix WinNonlin was employed to derive PK metrics.
Relative to healthy comparators, individuals with moderate impairment showed notably reduced exposure and faster removal of FospropofolFP: the AUC dropped by about 43%, while clearance increased roughly 60%. Severe impairment resulted in an AUC reduction of approximately 55%. In contrast, the active metabolite propofol displayed slower elimination, with clearance falling nearly 15% in moderate impairment and around 33% in severe impairment. Multivariate modeling indicated that preoperative albumin (ALB) independently predicted FospropofolFP exposure. This study provides the first evidence that moderate-to-severe hepatic dysfunction alters FospropofolFP disposition, producing the unusual combination of accelerated parent-drug elimination and delayed clearance of propofol. ALB emerged as an independent PK determinant. No unexpected safety concerns were observed after a single dose, though repeated administration warrants additional investigation.
