gms | German Medical Science

Introduction: We evaluated the microdialysis technique for pharmacokinetic studies within the BMBF-project „alternatives of animal experiments“. Microdialysis allows direct in vivo assessment of tissue concentrations of drugs in organs via continuous perfusion of a microdialysis probe over hours, while animals have to be sacrificed at each single time point in conventional distribution studies. Microdialysis was established in an orthotopic model of pancreatic cancer, with the antineoplastic and antiangiogenic drug Suramin as test drug.

Material and methods: Ductal pancreatic cancer (DSL-6A/C1) was induced in 96 Lewis rats. Animals were randomized in 2 groups and received low-dose Suramin (10 mg/kg) or PBS, starting 4 weeks after tumor induction, weekly i.p. Suramin concentrations in pancreatic cancer tissue were assessed for 24 hours at 0, 4 and 8 weeks after treatment started. 12 animals were evaluated at each time point in the conventional distribution study arm; groups of 2 animals were sacrificed every 4 hours within the 24 hour period to harvest tissue samples. In the microdialysis group, only 4 animals were evaluated at each time point: the microdialysis probe was implanted into the tumor and Suramin concentrations were measured continuously over 24 hours. Primary tumor volume and dissemination (local tumor infiltration and distant metastasis) were assessed after 0, 4 and 8 weeks of therapy.

Results: Microdialysis determined increasing Suramin concentrations in pancreatic cancer tissue over the study period, which were comparable to the drug concentrations measured in the conventional distribution group (Table 1 [Tab. 1]). Tumor volume was significantly reduced after 8 weeks of treatment with Suramin, whereas low dose Suramin didn't influence tumor dissemination.

Conclusion: Microdialysis continuously determines tumor tissue concentrations of drugs in vivo. 24 hours could be monitored in a single animal, which meant that only one third of the animal numbers was needed in comparison to the conventional distribution study arm. Microdialysis may allow a significant reduction of animal numbers in future pharmacokinetic studies.