Tissue Penetration of Gemcitabine and Gemcitabine Phosphate Metabolites Following Gemcitabine Intravesical System Administration Versus Standard Intravesical Instillation in a Preclinical Minipig Model.

Intravesical instillation of gemcitabine is an effective treatment for non-muscle-invasive bladder cancer but is hampered by short indwelling times, which can limit tissue exposure and efficacy. Gemcitabine intravesical system (gem-iDRS; formerly TAR-200) is a novel intravesical drug-releasing system designed for prolonged local gemcitabine delivery within the bladder, offering the potential for sustained tissue penetration. We investigated the penetration, tissue distribution, and retention of gemcitabine and its active metabolites following gem-iDRS administration versus traditional intravesical instillation in a preclinical model. Five female minipigs received either a 2-h bolus gemcitabine hydrochloride (n = 3) intravesical instillation or insertion of gem-iDRS (n = 2) into the bladder. Bladder tissue regions and layers (dome, left and right lateral walls, and trigone) were collected at postinstillation time points and analyzed using liquid chromatography-tandem mass spectrometry. Following traditional intravesical gemcitabine instillation, active phosphorylated metabolites were detected across bladder layers at 2 h but were undetectable by 24 h. In contrast, gem-iDRS maintained measurable metabolite levels across bladder regions and layers for at least 96 h. This small sample size and the use of only healthy animals limit the generalizability of the findings to tumor-bearing bladder tissue. These findings demonstrate that gem-iDRS prolongs bladder tissue exposure compared with traditional intravesical instillation of gemcitabine. PATIENT SUMMARY: Our study compared two different ways of delivering gemcitabine (a chemotherapy drug) into the bladder of minipigs. We found that gem-iDRS (a new intravesical drug-releasing system) kept gemcitabine and active metabolites in the bladder tissue for a longer time than the traditional way of delivering gemcitabine.