PD27-11 PRELIMINARY PHARMACOKINETIC DATA OF AN IN VITRO AND ANIMAL STUDY OF A NOVEL INTRAVESICAL SUSTAINED DELIVERY SYSTEM OF LIDOCAINE AND OXYBUTYNIN (TRG-042)

Abstract

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology (PD27)1 Sep 2021PD27-11 PRELIMINARY PHARMACOKINETIC DATA OF AN IN VITRO AND ANIMAL STUDY OF A NOVEL INTRAVESICAL SUSTAINED DELIVERY SYSTEM OF LIDOCAINE AND OXYBUTYNIN (TRG-042) Boris Chertin, David Dothan, Nadav Malchi, Avi Gordon, and Dan Touitou Boris ChertinBoris Chertin More articles by this author , David DothanDavid Dothan More articles by this author , Nadav MalchiNadav Malchi More articles by this author , Avi GordonAvi Gordon More articles by this author , and Dan TouitouDan Touitou More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002020.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Interstitial Cystitis / Bladder pain syndrome (IC/BPS) is a chronic debilitating condition of unknown etiology. Intravesical lidocaine administration has demonstrated pain relief in patients with IC/BPS. Intravesical administration of Oxybutynin has a well-documented therapeutic effect in patients with urinary bladder disorders due to a direct local anesthetic, antimuscarinic and spasmolytic effect within the bladder wall. However, intravesical use of the both drugs in the clinical practice did not stand the test of time due to rapid dilution and loss of drug with urination requiring multiple administrations. The ability to prolong drug retention in the urinary bladder enhances the bladder wall tissue exposure to adequate therapeutic level of drugs. The aim of this study was to evaluate the efficacy and safety of fixed-dose combination of Lidocaine and Oxybutynin novel polymeric composition forming instantly in the urine a sustained delivery system named TRG-042. METHODS: We have In-Vitro tested release of Lidocaine and Oxybutynin from TRG-042 in artificial urine (AUF) and have quantitatively determined Oxybutynin and Lidocaine concertation utilizing high-pressure liquid chromatography(HPLC). Following the successful In-Vitro study weekly formulation of TRG-042 was instilled into urinary bladder of 6 pigs. All pigs were followed with cystoscopy and US in order to assess the gradual degradation of the intravesical delivery system and to evaluate the response of the bladder over the seven days. Daily blood samples were tested for drug quantitation. Three pigs, who received TRG-042 without Oxybutynin and Lidocaine served as a control. RESULTS: In-Vitro studies have demonstrated Oxybutynin and Lidocaine sustained release over the one-week period coupled with the full degradation of the matrix. None of the animals demonstrated any side effects following instillation. Cystoscopy examination observed gradual disintegration of the TRG-042 over one-week period with no adverse reaction of the bladder mucosa. Plasma concentrations of Oxybutynin and Lidocaine were uniformly high and stable over the one-week study period 1.46+/-0.176 ng/ml and 4.29+/-2.48 ng/ml respectively (mean+/-SEM) with almost undetectable concentration of active metabolite N-desethyloxybutynin (NDO) 0.032+/-0.068 ng/ml. CONCLUSIONS: The In-Vitro and animal data suggest that TRG-042 can safely be used for possible intravesical sustain release of Lidocaine and Oxybutynin in the treatment of BPS/IC. Our preliminary results should be further confirmed in clinical studies. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e448-e448 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Boris Chertin More articles by this author David Dothan More articles by this author Nadav Malchi More articles by this author Avi Gordon More articles by this author Dan Touitou More articles by this author Expand All Advertisement Loading ...