Ropivacaine gel in active distal ulcerative colitis and proctitis -- a pharmacokinetic and exploratory clinical study.
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 ulcerative colitis.
Arlander
E
E
Department of Clinical Pharmacology, Astra Pain Control AB, Sodertaelje, Sweden.
Ost
A
A
Stahlberg
D
D
Lofberg
R
R
D000285:Administration, Rectal; D000293:Adolescent; D000328:Adult; D000368:Aged; D000577:Amides / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011349:Proctitis / Q000188:drug therapy / Q000378:metabolism*; D000077212:Ropivacaine
D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine