Intravesical sustained release system of lidocaine and oxybutynin results from in vitro and animal study.
Bladder pain syndrome
Interstitial Cystitis
Lidocaine
Oxybutynin
Sustained release
TRG-042
Journal
International urology and nephrology
ISSN: 1573-2584
Titre abrégé: Int Urol Nephrol
Pays: Netherlands
ID NLM: 0262521
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
received:
07
03
2022
accepted:
01
06
2022
pubmed:
4
7
2022
medline:
16
8
2022
entrez:
3
7
2022
Statut:
ppublish
Résumé
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic debilitating condition of unknown etiology. Intravesical lidocaine demonstrated pain relief in patients with IC/BPS. Intravesical oxybutynin has shown therapeutic efficacy in patients with urinary bladder disorders. However, loss of drug with urination requiring multiple administrations and immediate dilution of drug concentration by residual urine in the bladder mitigated intravesical use of both drugs in clinical practice. The aim of this study was to evaluate the efficacy and safety of fixed-dose combination of lidocaine and oxybutynin, forming in the urine a sustained delivery system named TRG-042. In-vitro, we have quantitatively tested the concentration of lidocaine and oxybutynin released from TRG-042 in artificial urine. Following the successful in-vitro study weekly formulation of TRG-042 was instilled intravesically to six pigs. All pigs were followed with cystoscopy to assess the gradual degradation of the delivery system and to evaluate bladder response over 7 days. Daily blood samples were tested for drug quantization. In-vitro studies have demonstrated oxybutynin and lidocaine sustained release over 1-week period coupled with full degradation of the matrix. None of the animals demonstrated any side effects following instillation. Cystoscopy examination observed gradual disintegration of TRG-042 over 1-week with no adverse reaction to the mucosa. Plasma concentrations of oxybutynin and lidocaine were uniformly stable over the 1-week period [1.46 ± 0.176 ng/ml and 4.29 ± 2.48 ng/ml respectively(mean ± SEM)] with almost undetectable concentration of N-desethyloxybutynin (NDO)[0.032 ± 0.068 ng/ml]. The in-vitro and animal data demonstrated that TRG-042 can safely be used for intravesical sustained release of lidocaine and oxybutynin in the treatment of BPS/IC.
Identifiants
pubmed: 35780464
doi: 10.1007/s11255-022-03280-8
pii: 10.1007/s11255-022-03280-8
doi:
Substances chimiques
Delayed-Action Preparations
0
Mandelic Acids
0
Lidocaine
98PI200987
oxybutynin
K9P6MC7092
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2167-2174Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature B.V.
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