No volume effect on retrograde colonic spread of rectally-administered ropivacaine gel.
BACKGROUND
Rectal administration of enemas, foams and suppositories is the most efficient way to deliver locally acting drugs to the distal colon. Ropivacaine, a long-acting local anaesthetic, was chosen as a candidate for a new rectal treatment of ulcerative colitis.


OBJECTIVE
To determine the colonic spread of a rectal ropivacaine formulation.


METHODS
In this randomized, incomplete cross-over study, 12 male volunteers were given 200 mg ropivacaine HCl rectally in 20, 40, 60 and 80 mL hydroxypropyl methylcellulose gel. The viscosity of the gel was 1.1 Pa s. The spread of the radiolabelled (99mTc-labelled diethylenetriaminepenta-acetic acid) formulations was assessed by gamma-scintigraphy. Plasma was collected and analysed for ropivacaine base.


RESULTS
The retrograde spread was limited to the descending colon and the difference between the studied volumes was not statistically significant. Only the 80-mL volume tended to have a larger distribution, although the 20-mL volume showed the same maximal distribution in two subjects. No distinct relationship between volume, retrograde colonic spread and plasma concentrations could be found. Ropivacaine was well tolerated.


CONCLUSIONS
Rectal ropivacaine gel in all volumes between 20 and 80 mL can spread up to the descending colon. There was no relationship between either retrograde colonic spread or the administered volume and the ropivacaine plasma concentrations.
Arlander
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E
Experimental Medicine, AstraZeneca R&D, Södertälje, Sweden.eva-arlander@astrazeneca.com
Cederlund
T
T
Måre
K
K
D000285:Administration, Rectal; D000328:Adult; D000577:Amides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003106:Colon / Q000378:metabolism; D018592:Cross-Over Studies; D005782:Gels; D006801:Humans; D008297:Male; D000077212:Ropivacaine
D000577:Amides; D000779:Anesthetics, Local; D005782:Gels; D000077212:Ropivacaine