Pharmacokinetics of Repeated Melatonin Drug Administrations Prior to and After Surgery

Nathja Groth Harpsøe, Lars Peter Kloster Andersen, Louise Vennegaard Mielke, Bo Jønsson, Morten Troels Jenstrup, Ismail Gögenur, Jacob Rosenberg

Publikation: Bidrag til tidsskriftArtikelForskningpeer review


Background: Recent clinical studies have documented the analgesic, anti-inflammatory, antioxidative and anxiolytic effects of exogenous melatonin. The pharmacokinetic properties of melatonin have primarily been investigated in experimental studies. Objective: The aim of this study was to estimate the pharmacokinetics of melatonin in patients undergoing surgery and general anesthesia. Methods: The study was designed as a prospective, two-phase cohort study. Patients were candidates for subpectoral breast augmentation surgery, and surgical procedures were performed by a single surgeon. The perioperative treatment protocol was standardized between patients. During the study, each patient received two separate oral administrations of melatonin 10 mg. Melatonin was administered 60 min before surgery, and at 9:00 p.m. the evening after surgery. The pharmacokinetic variables absorption half-life (t½ absorption), time to maximal plasma concentration (Tmax), maximal plasma concentration (Cmax), elimination half-life (t½ elimination), and area under the melatonin plasma concentration-time curve from time zero to infinity (AUC) were estimated for both study phases. Results: Median (interquartile range) values of t½ absorption and Tmax were significantly increased during the postoperative phase [10.8 (6.9–15.1) min; 90.0 (48.8–120.0) min] compared with perioperatively [9.5 (6.3–16.5) min; 30.0 (15.0–30.0) min] (p = 0.034; p = 0.002), respectively. Cmax values were significantly higher during surgery [5497.5 (2077.1–13,233.8) pg/ml] compared with postoperative values [2340.5 (1672.4–8871.4) pg/ml] (p = 0.005). Correspondingly, t½ elimination was significantly extended during the postoperative phase [103.5 (57.8–237.8) min] compared with the perioperative phase [60.5 (47.8–83.6) min] (p = 0.015). AUC did not differ between the study phases (p > 0.05). Conclusions: These preliminary results indicate that postoperative melatonin dose should be augmented compared with preoperative administration if corresponding melatonin plasma levels are intended. Furthermore, postoperative administration times should be advanced compared with preoperative administration.

Sider (fra-til)1045-1050
Antal sider6
TidsskriftClinical Drug Investigation
Udgave nummer12
StatusUdgivet - 1 dec. 2016

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