BACKGROUND/AIMS: A reproducible, endoscope-based, large animal model, of acute pancreatitis was developed to meet the need for a suitable means of preclinically testing treatments. The aim of this study was to develop an endoscope-based animal model of acute pancreatitis. METHODS: This experimental study was conducted on six mini-pigs. The pancreatitis model was induced by infusing contrast medium (CM) or sodium taurocholate (TCA) under high pressure (100 mmHg) into the main pancreatic duct by endoscopic retrograde pancreatography. Animals were randomly allocated to three groups: a CM group, a 10% TCA group, and a 20% TCA group. Pancreatic injuries were evaluated histologically, and serum amylase and lipase levels were measured. RESULTS: Acute pancreatitis was observed in all animals during hematologic and histologic examinations. Serum amylase and lipase levels were significantly higher (> 10 times baseline), and pancreatic edema, vacuolization of acinar cells, and hemorrhagic necrosis were observed. Severity of pancreatitis tended to be greater in the TCA groups than in the CM group as assessed using histologic scores, and degrees of pancreatitis were found to be dose-dependently related to TCA concentration. CONCLUSIONS The two endoscopic procedures described are effective and safe for creating a swine model of acute pancreatitis. The authors hope the described endoscopic methods will assist in the development of a suitable treatment strategy.

PURPOSE: We planned to evaluate the toxicity and efficacy of DA-3030 to determine the recommended dose for phase III clinical trial based on the biologically active doses from phase I/II clinical trial. MATERIALS AND METHODS: Open non-randomized phase I/II study was carried out in 64 cancer patients with chemotheray-induced myelosuppression. After 1 cycle of control period (chemotherapy without DA-3030), DA-3030 was started 24 hours after the second cycle of chemotherapy to 4 groups of patients with the doses of 50 microgram/m2/day (step I), 100 microgram/m2/day (step II), 150 microgram/m2/day (step III), 200microgram/m2/day (step IV) by once-a-day subcutaneous administration for 10 days. RESULTS: Of the 64 enrolled patients, 46 patients were evaluable. Tmax reached after 2 hours of injection in step I and 4 hours in step II-IV. Terminal half life was 1.8 hours in step I and 3.2 hours in step II, 3.3 hours in step III, 3.0 hours in step IV. Area under the curve (AUC) and AUMC increased dose dependently from step I through step IV. Total clearance rate decreased in a dose dependent manner but the volume of distribution showed no differences between the steps.The mean nadir count of total WBC and neutrophil increased in all 4 steps of DA-3030 administration. Also the duration of leukopenia, equal to or less than 2,000/uL or neutropenia and the recovery time of WBC or neutrophil from nadir decreased with DA-3030 administration in all 4 steps. But no differece of DA-3030 effect was found among 4 steps. When we compared the clinical efficacy of DA-3030 with total WBC and neutrophil criteria, it was 58.3% and 58.3% in step I, 90.0% and 80.0% in step II, 91.7% and 91.7% in step III, 75.0% and 70.0% in step IV. Although the duration of antibiotics administration showed no difference between control and DA-3030 administration period in step I, it decreased with DA-3030 administration in step II-IV. Infection was found only in step I. Life-threatening side effect was not found in all steps. Only mild myalgia was found without any dose relationship. CONCLUSION: When we considered the efficacy, toxicity and pharmacokinetic parameters, we suggest that 100microgram/m2 is an appropriate dosage for the phase III clinical trial.
Anti-Bacterial Agents ; Drug Therapy* ; Half-Life ; Humans ; Leukopenia ; Myalgia ; Neutropenia* ; Neutrophils