title: The effect of liver esterases and temperature on remifentanil degradation in vitro.
abstract: Remifentanil is a potent opioid metabolized by serum and tissue esterases; it is routinely administered to patients with liver failure as anaesthetic and analgo-sedative without variation in doses, even if prolonged clinical effects and respiratory depression have been observed in these patients. The aim of this study was to determine remifentanil enzymatic degradation kinetics bearing in mind the effect of liver esterases in order to trace a more accurate pharmacokinetic profile of the drug. Solution samples were taken over time and analysed to measure remifentanil concentration by HPLC. We reproduced the physiological settings, varying temperature and pH in vitro and evaluated the kinetics of degradation of remifentanil in the presence of Rhizopus Oryzae esterases, equine liver esterases and porcine liver esterases. Remifentanil kinetics of degradation was accelerated by porcine liver esterases. Remifentanil in vitro half-life decreases with increasing temperatures in the presence of porcine liver esterases. A drug model simulation considering the effect of temperature in the presence of liver esterases was developed. Remifentanil in vitro half-life decreases with increasing temperatures when porcine liver esterases are present. In this paper we propose a model for describing remifentanil degradation kinetics at various temperatures.
authors.affiliation: Department of Medicine, University of Salerno, Baronissi, Italy. Electronic address: opiazza@unisa.it.
authors.forename: Ornella
authors.initials: O
authors.lastname: Piazza
authors.affiliation: Department of Industrial Engineering, University of Salerno, Fisciano, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Cascone
authors.affiliation: Department of Medicine, University of Salerno, Baronissi, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Sessa
authors.affiliation: Department of Medicine, University of Naples "Federico II", Napoli, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: De Robertis
authors.affiliation: Department of Industrial Engineering, University of Salerno, Fisciano, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Lamberti
mesh_terms: D000701:Analgesics, Opioid / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D004950:Esterases / Q000378:metabolism*; D006736:Horses; D006993:Hypnotics and Sedatives / Q000378:metabolism / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D010880:Piperidines / Q000378:metabolism* / Q000494:pharmacology; D000077208:Remifentanil; D013552:Swine; D013696:Temperature
chemical_list: D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D010880:Piperidines; D004950:Esterases; D000077208:Remifentanil
keywords: HPLC; Liver esterases; Plasma esterases; Remifentanil pharmacokinetics