Systemic Absorption and Pharmacokinetics of Single-dose Intravesical Gemcitabine After Transurethral Resection of the Bladder in Non-muscle-invasive Bladder Cancer

Massimo Maffezzini, Fabio Campodonico, Matteo Puntoni, Antonietta Martelli, Francesca Mattioli

Research output: Contribution to journalArticle

Abstract

Objectives: To evaluate the systemic quantitative absorption, pharmacokinetics, and toxicities of gemcitabine administered intravesically at the recommended, high-concentration dose of 40 mg/mL, immediately after transurethral resection. Methods: For a single intravesical instillation of gemcitabine after resection, 15 consecutive patients with recurrent, low-, or intermediate-risk non-muscle-invasive bladder cancer candidates were selected. The extent of resection was defined as "small" if ≤ 6 excursions of the resecting loop and "large" if > 6 excursions were needed to eliminate lesions. Eight and 7 patients, underwent a small and a large resection, respectively. Immediately after surgery 2000 mg of gemcitabine in 50 mL saline was instilled and held in the bladder for 1 hour. Pharmacokinetics of gemcitabine and its metabolite 2′,2′-difluorodeoxyuridine were determined in plasma by high-performance liquid chromatography. Local and systemic toxicity were assessed. Results: The highest mean gemcitabine concentrations were 1.38 μg/mL in small and 2.47 μg/mL in large resections. The difference was largest at 15 minutes after instillation (1.10 vs 2.47 μg/mL, P = .001). A significant difference was found between time and type of resection for gemcitabine plasma levels (P = .02) but not for 2′,2′-difluorodeoxyuridine. Toxicity never exceeded grade 2. At a mean follow-up of 2 years, 9 patients (60%) were found to be recurrence-free. Conclusions: The systemic absorption of a single postoperative intravesical instillation of high concentration gemcitabine is proportional to the extent of resection; peak plasma concentrations reached at 15 minutes are below the levels of intravenous administration.

Original languageEnglish
Pages (from-to)1078-1083
Number of pages6
JournalUrology
Volume74
Issue number5
DOIs
Publication statusPublished - Nov 2009

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gemcitabine
Urinary Bladder Neoplasms
Urinary Bladder
Pharmacokinetics
Intravesical Administration
Physiological Absorption
Intravenous Administration
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Urology

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Systemic Absorption and Pharmacokinetics of Single-dose Intravesical Gemcitabine After Transurethral Resection of the Bladder in Non-muscle-invasive Bladder Cancer. / Maffezzini, Massimo; Campodonico, Fabio; Puntoni, Matteo; Martelli, Antonietta; Mattioli, Francesca.

In: Urology, Vol. 74, No. 5, 11.2009, p. 1078-1083.

Research output: Contribution to journalArticle

Maffezzini, Massimo ; Campodonico, Fabio ; Puntoni, Matteo ; Martelli, Antonietta ; Mattioli, Francesca. / Systemic Absorption and Pharmacokinetics of Single-dose Intravesical Gemcitabine After Transurethral Resection of the Bladder in Non-muscle-invasive Bladder Cancer. In: Urology. 2009 ; Vol. 74, No. 5. pp. 1078-1083.
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