1. The effect of liver esterases and temperature on remifentanil degradation in vitro
- Author
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Edoardo De Robertis, Linda Sessa, Ornella Piazza, Sara Cascone, Gaetano Lamberti, Piazza, Ornella, Cascone, Sara, Sessa, Linda, DE ROBERTIS, Edoardo, and Lamberti, Gaetano
- Subjects
Remifentanil pharmacokinetics ,Liver esterases ,Plasma esterases ,HPLC ,Swine ,Kinetics ,Rhizopus oryzae ,Remifentanil ,Pharmaceutical Science ,Pharmacology ,High-performance liquid chromatography ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Piperidines ,030202 anesthesiology ,medicine ,Animals ,Hypnotics and Sedatives ,030212 general & internal medicine ,Horses ,Respiratory system ,Liver esterase ,biology ,Chemistry ,Esterases ,Temperature ,biology.organism_classification ,In vitro ,Analgesics, Opioid ,Opioid ,Liver ,Plasma esterase ,medicine.drug - 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.
- Published
- 2016