Effects of intraduodenal versus intragastric administration of quinine on gut function in healthy, lean volunteers.

Subjects will receive in randomised, double-blind fashion, a 600mg bolus administration of quinine either intraduodenally or intragastrically on 2 separate visits. Each visit will last 5hrs in duration, and will be separated by 3-7 days. Visits will be carried out in the Adelaide Medical School, University of Adelaide, by staff members trained in the required clinical research facilities. Subjects will consume a standardised dinner meal, a 400g McCain's beef lasagne, the night before both study visits by no later than 7pm. After fasting for 14 hours overnight and refraining from alcohol and exercise for 24 hours, subjects will arrive at the clinical research facility by 8:30am. Upon arrival, subjects will be intubated with a 17-channel manometric catheter (Dentsleeve, Mui Scientific) that will be inserted through an anaesthetised nostril and allowed to pass through the stomach and into the duodenum by peristalsis. The manometric catheter consists of 16 side holes spaced at 1.5 cm intervals, measuring pressures in the antrum, pylorus, and duodenum (APD pressures). The most proximal antral channel (with the side hole positioned approximately 9cm proximal to the pylorus when the catheter is in position) is used for intragastric administration. An additional channel (with the side hole positioned approximately 14 cm distal to the pylorus when the catheter is in position) is used for intraduodenal administration. The correct positioning of the catheter will be maintained by continuous measurement of the transmucosal potential difference (TMPD) between the most distal antral channel and the most proximal duodenal channel. All manometric channels will be perfused with degassed, distilled water, except for the two TMPD channels, which will be perfused with degassed 0.9% saline, at 0.15 ml/min. An intravenous cannula will be placed into a right forearm vein for regular blood sampling to measure plasma hormone concentrations. Once the catheter has been positioned correctly, fasting motility will be monitored continuously, and immediately after the end of phase III activity of the fasting migrating motor complex (MMC), during a period of motor quiescence (t=-10 - 0 min), a 9 ml venous blood sample (baseline) will be taken, and the subject will complete a 100mm visual analogue scale questionnaire (VAS) to assess appetite-related perceptions (fullness, hunger, etc.) and GI symptoms (nausea and bloating). At t = -1 min, either the intraduodenal or intragastric bolus of quinine will be administered and another blood sample and VAS questionnaire will be taken immediately after administration. Regular 9ml venous blood samples will be taken throughout the study and additional VAS completed. A total of 90ml of blood will be taken on each study day (180ml over both study visits).