IngentaConnect Ropivacaine gel in active distal ulcerative colitis and proctitis...

Abstract:

Background: Local anaesthetics have anti-inflammatory effects as indicated by preclinical and explorative clinical data.

Objective: To investigate the pharmacokinetics, tolerability and clinical efficacy of the new local anaesthetic ropivacaine in active distal ulcerative colitis.

Methods: Twelve patients were openly given 200 mg ropivacaine gel rectally twice daily for 2 weeks in this open study.

Results: Mean peak total plasma concentrations, Cmax, were 1.37, 1.26, 1.03 and 0.99 mg/L on treatment days 1, 3, 7 and 14. The mean unbound plasma concentrations at Cmax were 0.071, 0.058, 0.050 and 0.045 mg/L. The decrease in Cmax (P<0.01) as well as in the area under the plasma concentration-time curve, AUC (P<0.01), may be due to a decreased absorption but an increased metabolism cannot be excluded. The median time of Cmax was around 2 h and the mean terminal half-life was around 2.7 h. Mucosal inflammation assessed endoscopically at the most severely affected site decreased after 2 weeks of treatment (P<0.01; blinded) and there was also a trend towards histological improvement (P=0.06). Clinical symptoms, including total number of stools, blood in stools and diarrhoea increased (P<0.05) during the study. The treatment was, in general, well tolerated with few gastrointestinal complaints and there were no unequivocal signs of systemic effects.

Conclusions: Ropivacaine given rectally as a gel, 200 mg twice daily does not accumulate over a 2-week treatment period and carries a low risk for systemic adverse effects. The results suggest a therapeutic efficacy in active distal ulcesative colitis.

Document Type: Research article

Affiliations: 1: Department of Clinical Pharmacology, Astra Pain Control AB, Sodertalje 2: Department of Pathology, Karolinska Hospital, Stockholm 3: Unit of Gastroenterology, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden

Ropivacaine gel in active distal ulcerative colitis and proctitis-a pharmacokinetic and exploratory clinical study