Abstract
INTRODUCTION: Gemcitabine is a deoxycytidine analogue, used intravenously in the treatment of several tumours, including transitional cell carcinoma of the bladder. It has been shown to be effective and well tolerated when given systemically. We investigated the use of this agent administered intravesically in pigs for histological studies of the bladder and pharmacokinetic research. MATERIAL AND METHODS: Two groups of 5 female pigs each received once 175mg and 350mg gemcitabine intravesically for 2 hours. A third group of 5 pigs received 350mg gemcitabine weekly for 6 weeks. Animals were observed for clinical signs of toxicity. Blood was withdrawn for gemcitabine pharmacokinetics and in group 3 also for peripheral blood counts. The animals were euthanized 24 hours after (the last) instillation. Histological examination of the bladder wall was performed. RESULTS: Doses of 175 and 350mg gemcitabine were well tolerated. The animals showed no signs of deterioration of their well-being. Peripheral blood counts showed no signs of immunosuppression in the third group. In none of the pigs systemic absorption was seen, up to 4 hours after the beginning of instillation. Histology showed in all cases normal bladder wall histology, except for some cases with mild signs of infection (mainly group 3). CONCLUSION: The use of gemcitabine as an intravesical agent in pigs is well tolerated, has no bladder toxicity and is not absorbed systemically.
