Sandip M Prasad, Michael J Louie, Brent Burger, Victoria Tsurutis, Nikky Ugwuoke, Dalit Strauss-Ayali
{"title":"UGN - 102的药代动力学研究，UGN - 102是一种含有丝裂霉素的逆热凝胶，用于治疗非肌肉浸润性膀胱癌。","authors":"Sandip M Prasad, Michael J Louie, Brent Burger, Victoria Tsurutis, Nikky Ugwuoke, Dalit Strauss-Ayali","doi":"10.1007/s00280-025-04821-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the pharmacokinetic properties of UGN-102, a mitomycin-containing reverse thermal gel.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 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 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 mg or 10 mg mitomycin, respectively, and 10-fold lower than the RMTL. Maximum measured urine concentration was 635 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 h and mean AUC<sub>0-6</sub> 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.</p><p><strong>Conclusions: </strong>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><p><strong>Study registration: </strong>BL004: NCT02307487; BL005: NCT03558503.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"100"},"PeriodicalIF":2.3000,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetics of UGN‑102, an investigational mitomycin‑containing reverse thermal gel for the treatment of non-muscle invasive bladder cancer.\",\"authors\":\"Sandip M Prasad, Michael J Louie, Brent Burger, Victoria Tsurutis, Nikky Ugwuoke, Dalit Strauss-Ayali\",\"doi\":\"10.1007/s00280-025-04821-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>To evaluate the pharmacokinetic properties of UGN-102, a mitomycin-containing reverse thermal gel.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 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 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 mg or 10 mg mitomycin, respectively, and 10-fold lower than the RMTL. Maximum measured urine concentration was 635 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 h and mean AUC<sub>0-6</sub> 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.</p><p><strong>Conclusions: </strong>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><p><strong>Study registration: </strong>BL004: NCT02307487; BL005: NCT03558503.</p>\",\"PeriodicalId\":9556,\"journal\":{\"name\":\"Cancer Chemotherapy and Pharmacology\",\"volume\":\"95 1\",\"pages\":\"100\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-10-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Chemotherapy and Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00280-025-04821-5\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Chemotherapy and Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00280-025-04821-5","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
Pharmacokinetics of UGN‑102, an investigational mitomycin‑containing reverse thermal gel for the treatment of non-muscle invasive bladder cancer.
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.
期刊介绍：
Addressing a wide range of pharmacologic and oncologic concerns on both experimental and clinical levels, Cancer Chemotherapy and Pharmacology is an eminent journal in the field. The primary focus in this rapid publication medium is on new anticancer agents, their experimental screening, preclinical toxicology and pharmacology, single and combined drug administration modalities, and clinical phase I, II and III trials. It is essential reading for pharmacologists and oncologists giving results recorded in the following areas: clinical toxicology, pharmacokinetics, pharmacodynamics, drug interactions, and indications for chemotherapy in cancer treatment strategy.
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