Melatonin and Clonidine Premedication Has Similar Impact on the Pharmacokinetics and Pharmacodynamics of Propofol Target Controlled-Infusions

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 E-max 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.