Biomaterial Database

No volume effect on retrograde colonic spread of rectally-administered ropivacaine gel. 2003

E Arlander, and T Cederlund, and K Måre

Experimental Medicine, AstraZeneca R&D, Södertälje, Sweden.eva-arlander@astrazeneca.com

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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D003093	Colitis, Ulcerative	Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.	Colitis Gravis,Idiopathic Proctocolitis,Inflammatory Bowel Disease, Ulcerative Colitis Type,Ulcerative Colitis
D003106	Colon	The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON.	Appendix Epiploica,Taenia Coli,Omental Appendices,Omental Appendix,Appendices, Omental,Appendix, Omental
D005782	Gels	Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquefies; the resulting colloid is called a sol.
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077212	Ropivacaine	An anilide used as a long-acting local anesthetic. It has a differential blocking effect on sensory and motor neurons.	1-Propyl-2',6'-pipecoloxylidide,AL 381,AL-381,LEA 103,LEA-103,Naropeine,Naropin,Ropivacaine Hydrochloride,Ropivacaine Monohydrochloride,Ropivacaine Monohydrochloride, (S)-isomer,1 Propyl 2',6' pipecoloxylidide,AL381,LEA103
D000285	Administration, Rectal	The insertion of drugs into the rectum, usually for confused or incompetent patients, like children, infants, and the very old or comatose.	Anal Drug Administration,Drug Administration, Rectal,Instillation, Rectal,Rectal Drug Administration,Drug Administration, Anal,Rectal Administration,Administration, Anal Drug,Administration, Rectal Drug,Administrations, Anal Drug,Administrations, Rectal,Administrations, Rectal Drug,Anal Drug Administrations,Drug Administrations, Anal,Drug Administrations, Rectal,Instillations, Rectal,Rectal Administrations,Rectal Drug Administrations,Rectal Instillation,Rectal Instillations
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D000577	Amides	Organic compounds containing the -CO-NH2 radical. Amides are derived from acids by replacement of -OH by -NH2 or from ammonia by the replacement of H by an acyl group. (From Grant & Hackh's Chemical Dictionary, 5th ed)	Amide
D000779	Anesthetics, Local	Drugs that block nerve conduction when applied locally to nerve tissue in appropriate concentrations. They act on any part of the nervous system and on every type of nerve fiber. In contact with a nerve trunk, these anesthetics can cause both sensory and motor paralysis in the innervated area. Their action is completely reversible. (From Gilman AG, et. al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed) Nearly all local anesthetics act by reducing the tendency of voltage-dependent sodium channels to activate.	Anesthetics, Conduction-Blocking,Conduction-Blocking Anesthetics,Local Anesthetic,Anesthetics, Topical,Anesthetic, Local,Anesthetics, Conduction Blocking,Conduction Blocking Anesthetics,Local Anesthetics,Topical Anesthetics