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Purpose <p>To evaluate the pharmacokinetic properties of UGN-102, a mitomycin-containing reverse thermal gel.</p> Methods <p>Twelve patients with NMIBC received 6 once-weekly intravesical instillations of UGN-102 (BL004: 120&#xa0;mg mitomycin [<i>n</i> = 6]; BL005: 75&#xa0;mg mitomycin [<i>n</i> = 6]). Plasma samples for determination of pharmacokinetic (PK) parameters were collected up to 6&#xa0;h following instillation.</p> Results <p>In BL004, mean C<sub>max</sub> was 20.39 ng/mL, and median was 16.10 ng/mL (range 4.00–40.40), 100-10-fold lower than reported myelosuppression toxic level (RMTL); and median T<sub>max</sub> was 1.5&#xa0;h. Mean AUC<sub>0-6</sub> was 56.23 ng·h/mL and mean apparent terminal half-life (t<sub>1/2</sub>) was 49&#xa0;min. The highest observed C<sub>max</sub> (40.40 ng/mL) was 59-fold and 13-fold lower than C<sub>max</sub> following IV 30&#xa0;mg or 10&#xa0;mg mitomycin, respectively, and 10-fold lower than the RMTL. Maximum measured urine concentration was 635&#xa0;µg/mL. In BL005, mean C<sub>max</sub> was 2.27 ng/mL, 181-fold lower than the RMTL; mean T<sub>max</sub> was 1.95&#xa0;h and mean AUC<sub>0–6</sub> was 5.69 ng·h/mL. At 4–6&#xa0;h post intravesical instillation, mitomycin concentrations in urine were either below or approaching the lower level of quantification (&lt; 0.250&#xa0;µg/mL) in 5/6 patients. In the remaining patient, the measurable urine concentrations over the 6-hour period suggest dwell time was &gt; 6&#xa0;h post-instillation, possibly due to the tumor location restricting urine flow. However systemic exposure was &lt; 4 ng/mL, 100-fold lower than the RMTL.</p> Conclusions <p>Intravesical instillation of UGN-102 results in low-level systemic absorption of mitomycin, with C<sub>max</sub> values considerably lower than those following IV administration and those associated with myelosuppression.</p> Study registration <p>BL004: NCT02307487; BL005: NCT03558503.</p>

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Pharmacokinetics of UGN‑102, an investigational mitomycin‑containing reverse thermal gel for the treatment of non-muscle invasive bladder cancer

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  • 发表日期：

    2025年10月11日

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  • Sandip M. Prasad,
  • Michael J. Louie,
  • Brent Burger,
  • Victoria Tsurutis,
  • Nikky Ugwuoke,
  • Dalit Strauss-Ayali

摘要

Purpose

To evaluate the pharmacokinetic properties of UGN-102, a mitomycin-containing reverse thermal gel.

Methods

Twelve patients with NMIBC received 6 once-weekly intravesical instillations of UGN-102 (BL004: 120 mg mitomycin [n = 6]; BL005: 75 mg mitomycin [n = 6]). Plasma samples for determination of pharmacokinetic (PK) parameters were collected up to 6 h following instillation.

Results

In BL004, mean Cmax was 20.39 ng/mL, and median was 16.10 ng/mL (range 4.00–40.40), 100-10-fold lower than reported myelosuppression toxic level (RMTL); and median Tmax was 1.5 h. Mean AUC0-6 was 56.23 ng·h/mL and mean apparent terminal half-life (t1/2) was 49 min. The highest observed Cmax (40.40 ng/mL) was 59-fold and 13-fold lower than Cmax following IV 30 mg or 10 mg mitomycin, respectively, and 10-fold lower than the RMTL. Maximum measured urine concentration was 635 µg/mL. In BL005, mean Cmax was 2.27 ng/mL, 181-fold lower than the RMTL; mean Tmax was 1.95 h and mean AUC0–6 was 5.69 ng·h/mL. At 4–6 h post intravesical instillation, mitomycin concentrations in urine were either below or approaching the lower level of quantification (< 0.250 µg/mL) in 5/6 patients. In the remaining patient, the measurable urine concentrations over the 6-hour period suggest dwell time was > 6 h post-instillation, possibly due to the tumor location restricting urine flow. However systemic exposure was < 4 ng/mL, 100-fold lower than the RMTL.

Conclusions

Intravesical instillation of UGN-102 results in low-level systemic absorption of mitomycin, with Cmax values considerably lower than those following IV administration and those associated with myelosuppression.

Study registration

BL004: NCT02307487; BL005: NCT03558503.