Ropivacaine gel in active distal ulcerative colitis and proctitis -- a pharmacokinetic and exploratory clinical study.
Aliment Pharmacol Ther
; 10(1): 73-81, 1996 Feb.
Article
in En
| MEDLINE
| ID: mdl-8871446
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 ulcerative colitis.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proctitis
/
Colitis, Ulcerative
/
Amides
/
Anesthetics, Local
Limits:
Adolescent
/
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Aliment Pharmacol Ther
Journal subject:
FARMACOLOGIA
/
GASTROENTEROLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
1996
Document type:
Article
Affiliation country:
Sweden