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Ropivacaine gel in active distal ulcerative colitis and proctitis—a pharmacokinetic and exploratory clinical study
Author(s) -
ARLANDER E.,
ÓST Å.,
STÅHLBERGS D.,
LÓFBERG R.
Publication year - 1996
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.1996.tb00179.x
Subject(s) - medicine , pharmacokinetics , ropivacaine , ulcerative colitis , tolerability , gastroenterology , area under the curve , anesthesia , proctitis , adverse effect , disease
SUMMARY 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, 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 concentrations 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 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 C max 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 ulcerative colitis.