title: Melatonin and clonidine premedication has similar impact on the pharmacokinetics and pharmacodynamics of propofol target controlled-infusions.
abstract: Recently oral melatonin has been proposed as an agent for premedication. In this study, we compared melatonin with clonidine, considering its anxiolytic properties as well as the influence of both agents on the pharmacokinetic, hypnotic, and hemodynamic effects of propofol during propofol-remifentanil total intravenous anesthesia (TIVA). The dataset under analysis included 32 patients scheduled for a functional endoscopic sinus surgery. The population pharmacokinetic modeling was done with NONMEM. The PK of propofol was described with a two-compartment disposition model, whereas the BIS and AAI were described with a sigmoidal Emax model linked with the propofol concentration via the biophase compartment. The anxiolytic effect was assessed by means of the visual analog scale for anxiety (VAS-A). The population PK/PD model was successfully developed to describe the data. No significant differences in the PK/PD of propofol were noted due to the premedication with clonidine and melatonin. Melatonin was less effective than clonidine in reducing patients' anxiety at the induction of anesthesia, whereas clonidine premedication was associated with greater decrease in heart rate and blood pressure. A decreased EC50 (2.47 vs. 3.17 mg/L) and increased slope (2.71 vs. 1.30) of the sigmoidal Emax relationship was observed for the AAI index, as compared with the BIS measurements.
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, ul. Marii Magdaleny 14, 61 - 861, Poznan, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bienert
authors.affiliation: Department of Anesthesiology and Intensive Therapy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, ul. Marii Skłodowskiej - Curie 9, 85-094, Bydgoszcz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wawrzyniak
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, ul. Hallera 107, 80-401, Gdansk, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Wiczling
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, ul. Marii Magdaleny 14, 61 - 861, Poznan, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Przybyłowski
authors.affiliation: Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, ul. Grunwaldzka 6, 60 - 780, Poznan, Poland.
authors.forename: Zenon J
authors.initials: ZJ
authors.lastname: Kokot
authors.affiliation: Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, ul. Grunwaldzka 6, 60 - 780, Poznan, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Matysiak
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, ul. Marii Magdaleny 14, 61 - 861, Poznan, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Pachutko
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, ul. Hallera 107, 80-401, Gdansk, Poland.
authors.forename: Martyna
authors.initials: M
authors.lastname: Józefowicz
authors.affiliation: Department of Anesthesiology and Intensive Therapy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, ul. Marii Skłodowskiej - Curie 9, 85-094, Bydgoszcz, Poland.|Department of Anesthesiology and Intensive Therapy, Poznan University of Medical Sciences, ul. Marii Magdaleny 14, 61 - 861, Poznan, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kusza
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, ul. Marii Magdaleny 14, 61 - 861, Poznan, Poland.
authors.forename: Edmund
authors.initials: E
authors.lastname: Grześkowiak
mesh_terms: D000284:Administration, Oral; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D001007:Anxiety / Q000209:etiology / Q000517:prevention & control* / Q000523:psychology; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D008875:Middle Aged; D008954:Models, Biological; D011044:Poland; D011292:Premedication; D015742:Propofol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D018686:Anesthetics, Intravenous; D014151:Anti-Anxiety Agents; D008550:Melatonin; D003000:Clonidine; D015742:Propofol
keywords: clonidine; melatonin; pharmacodynamics; pharmacokinetics; propofol