Pharmacokinetics of UGN-101, a mitomycin-containing reverse thermal gel instilled via retrograde catheter for the treatment of low-grade upper tract urothelial carcinoma

Purpose: To evaluate the pharmacokinetic properties of UGN-101, a mitomycin-containing reverse thermal gel used as primary chemoablative treatment for low-grade upper tract urothelial carcinoma (UTUC), in a subset of patients participating in a phase 3 clinical trial. Methods: Pharmacokinetic parameters (C_max, T_max, AUC_(0–6), λz, t_½, and AUC_inf) were evaluated in six participants (male or female, ≥ 18 years) with biopsy-proven, low-grade UTUC who received the first of 6 once-weekly instillations of UGN-101 to the renal pelvis and calyces via retrograde ureteral catheter. Plasma samples were collected prior to instillation and 30 min, 1, 2, 3, 4, 5, and 6 h post-instillation. Safety was assessed by laboratory evaluations, physical exam, and adverse event monitoring. Results: The mean age of the six participants was 69 years; most were male (5/6) and Caucasian (5/6). Mean (SD) C_max was 6.24 (4.11) ng/mL and mean T_max was 1.79 (1.89) hours after instillation. Mean apparent t_½ following instillation was 1.27 (0.63) hours. Mean total systemic exposure to mitomycin up to 6 h post-instillation was 20.30 (19.69) ng h/mL. At 6 h post-instillation, mitomycin plasma concentrations of 5/6 participants were < 2 ng/mL. There were no clinically important adverse events or changes in laboratory values in any participant after a single instillation of UGN-101. Conclusion: The reverse thermal gel formulation of UGN-101 is associated with higher concentration and extended dwell time of mitomycin in contact with the urothelium of the upper urinary tract while limiting systemic absorption of mitomycin. Registration: NCT02793128; registered June 8, 2016.