ROPIVACAINE GEL IN ACTIVE DISTAL ULCERATIVE-COLITIS AND PROCTITIS - APHARMACOKINETIC AND EXPLORATORY CLINICAL-STUDY

Citation
E. Arlander et al., ROPIVACAINE GEL IN ACTIVE DISTAL ULCERATIVE-COLITIS AND PROCTITIS - APHARMACOKINETIC AND EXPLORATORY CLINICAL-STUDY, Alimentary pharmacology & therapeutics, 10(1), 1996, pp. 73-81
Citations number
25
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Pharmacy","Gastroenterology & Hepatology
ISSN journal
0269-2813
Volume
10
Issue
1
Year of publication
1996
Pages
73 - 81
Database
ISI
SICI code
0269-2813(1996)10:1<73:RGIADU>2.0.ZU;2-W
Abstract
Background: Local anaesthetics have anti-inflammatory effects as indic ated by preclinical and explorative clinical data. Objective: To inves tigate 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 re ctally twice daily for 2 weeks in this open study. Results: Mean peak total plasma concentrations, C-max, were 1.37, 1.26, 1.03 and 0.99 mg/ L on treatment days 1, 3, 7 and 14. The mean unbound plasma concentrat ions at C-max were 0.071, 0.058, 0.050 and 0.045 mg/L. The decrease in C-max (P < 0.01) as well as in the area under the plasma concentratio n-time curve, AUC (P < 0.01), may be due to a decreased absorption but an increased metabolism cannot be excluded. The median time of C-max was around 2 h and the mean terminal half-life was around 2.7 h, Mucos al inflammation assessed endoscopically at the most severely affected site decreased after 2 weeks of treatment (P < 0.01; blinded) and ther e was also a trend towards histological improvement (P = 0.06). Clinic al symptoms, including total number of stools, blood in stools and dia rrhoea increased (P < 0.05) during the study. The treatment was, in ge neral, well tolerated with few gastrointestinal complaints and there w ere 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 u lcerative colitis.