Pharmacokinetics of oral and intravenous melatonin in healthy volunteers

BACKGROUND: The aim was to investigate the pharmacokinetics of oral and iv melatonin in healthy volunteers. METHODS: The study was performed as a cohort crossover study. The volunteers received either 10 mg oral melatonin or 10 mg intravenous melatonin on two separate study days. Blood samples were collected at different time points following oral administration and short iv infusion, respectively. Plasma melatonin concentrations were determined by RIA technique. Pharmacokinetic analyses were performed by “the method of residuals” and compartmental analysis. The pharmacokinetic variables: k(a), t(1/2 absorption), t(max), C(max), t(1/2 elimination,)AUC(0-∞), and bioavailability were determined for oral melatonin. C(max), t(1/2 elimination), V(d), CL and AUC(0-∞) were determined for intravenous melatonin. RESULTS: Twelve male volunteers completed the study. Baseline melatonin plasma levels did not differ significantly between the study days (P = 0.067). Mean (SD) t(1/2 absorption) of oral melatonin was 6.0 (3.1) min. Mean t(max) was 40.8 (17.8) min with a median (IQR) C(max) of 3550.5 (2500.5–8057.5) pg ml(-1). Mean t(1/2 elimination) was 53.7 (7.0) min. Median absolute bioavailability was 2.5 (1.7–4.7) %. Median C(max) after short iv infusion of melatonin was 389,875.0 (174,775.0–440,362.5) pg ml(-1). Mean t(1/2 elimination) was 39.4 (3.6) min, mean V(d) 1.2 (0.6) l kg(-1) and mean CL 0.0218 (0.0102) l min(-1) kg(-1). CONCLUSIONS: This cohort crossover study estimated pharmacokinetics of oral and iv melatonin, respectively in healthy volunteers. Bioavailability of oral melatonin was only 3 %. TRIAL REGISTRATION: Eudra-CT number: 2013-000205-23 (initial registration 27.03.2013). Clinicaltrials.gov Identifier: NCT01923974 (initial registration 08.08.2013)

Laparoscopic Roux-en-Y gastric bypass in super obese Göttingen minipigs

Background: The specific mechanisms behind weight loss and comorbidity improvements in obese patients after Roux-en-Y gastric bypass (RYGBP) are still poorly understood. The aim of this study was to establish and evaluate the feasibility of a long-term survival RYGBP model in super obese Göttingen minipigs in order to improve the translational potential relative to current animal models. Methods: Eleven Göttingen minipigs with diet-induced obesity underwent laparoscopic RYGBP and were followed up to 9 months after surgery. Intra- and post-operative complications, body weight (BW), food intake and necropsy data were recorded. Results: Five minipigs survived without complications to the end of the study. Four minipigs developed surgical related complications and were euthanized while two minipigs died due to central venous catheter related complications. BW and food intake is reported for the six minipigs surviving longer than 4.5 months post-surgery. Weight loss and reduced food intake was seen in all minipigs. After 2-3 months of weight loss, weight regain was evident in all but two minipigs which seemed to continue losing weight. Necropsy revealed some variation in the length of the alimentary, biliary and common limb between minipigs. Conclusion: The use of obese Göttingen minipigs as a translational RYGBP model is feasible and has potential for the study of RYGBP-related changes in gut function, type-2 diabetes and appetite regulation. Still, the surgical procedure is technically highly demanding in obese Göttingen minipigs and the peri-operative animal care and follow up requires close monitoring