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5. Disposition of 5-aminosalicylic acid by olsalazine and three mesalazine preparations in patients with ulcerative colitis: comparison of intraluminal colonic concentrations, serum values, and urinary excretion

Author

Laursen, L. Staerk, Stokholm, M., Bukhave, K., Rask-Madsen, J., and Lauritsen, K.

Subjects
Sulfasalazine -- Health aspects, Aminosalicylic acids -- Health aspects, Olsalazine -- Health aspects, Ulcerative colitis -- Care and treatment, Health
Abstract

Sulfasalazine is a drug that is chemically related to aspirin and used in the treatment of ulcerative colitis. Oral sulfasalazine is broken down into two metabolites in the lower digestive tract. Of these, 5-aminosalicylic acid (5-ASA) is the therapeutically active product. Since the discovery that 5-ASA (which by itself is not orally active) is the active molecule, a variety of drug delivery strategies have been developed to chemically link 5-ASA with other molecules, and coated capsules and slow-release formulations have been designed to get the 5-ASA into the large intestine where it acts on the luminal side of the colon (inside the digestive tract). Intestinal absorption of 5-ASA occurs, but increased blood levels of the drug do not confer any additional therapeutic benefit and may, in fact, be toxic to the kidney. Fourteen patients with ulcerative colitis in remission took part in a study to evaluate the ability of several different formulations of 5-ASA-containing preparations to increase colonic concentrations of the drug. Each subject received a novel formulation (olsalazine; disodium azodisalicylate), both as coated tablets and gel capsules, and three other commercially available mesalazine formulations (Asacol, Pentasa, or Salofalk). Colonic and blood levels, as well as urinary excretion, of 5-ASA were determined after five days of each treatment. Olsalazine treatment doubled the colonic concentration of 5-ASA compared with Pentasa and Salofalk but not with Asacol; blood levels and urinary excretion of 5-ASA were decreased compared with the mesalazines. This indicates that olsalazine is one of the best vehicles for delivering 5-ASA to its site of action, while reducing the systemic concentrations of the drug that may be harmful to the kidney. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1990

10. Selective 5-lipoxygenase inhibition in ulcerative colitis

Author

Laursen, L. Staerk, Naesdal, J., Bukhave, K., Lauritsen, K., and Rask-Madsen, J.

Subjects
Ulcerative colitis -- Drug therapy, Colitis -- Drug therapy, Inflammation -- Mediators, Leukotrienes -- Physiological aspects
Published
1990

21. Eicosanoids and the intestine

Author

Edited by Peter Curtis-Prior, null, Bukhave, K., Rask-Madsen, J., Edited by Peter Curtis-Prior, null, Bukhave, K., and Rask-Madsen, J.

Published
2004

28. Effects of topical ropivacaine on eicosanoids and neurotransmitters in the rectum of patients with distal ulcerative colitis

Author

Hillingsø, J G, Kjeldsen, J, Schmidt, P T, Rasmussen, T N, Fisher-Hansen, B, Holst, Jens Juul, Lauristen, K, Bukhave, K, Rask-Madsen, J, Hillingsø, J G, Kjeldsen, J, Schmidt, P T, Rasmussen, T N, Fisher-Hansen, B, Holst, Jens Juul, Lauristen, K, Bukhave, K, and Rask-Madsen, J

Abstract

BACKGROUND: Topical administration of lidocaine has been suggested to have beneficial clinical effects in patients with active ulcerative colitis, but the mechanism of action, if any, remains obscure. As local anaesthetics may exert anti-inflammatory actions through their inhibition of nervous reflexes, we have studied the local effects of a single rectal dose of ropivacaine gel on rectal concentrations of eicosanoids and neurotransmittors in patients with relapsing ulcerative colitis.METHODS: In a randomized, double-blind, placebo-controlled study, concentrations of leukotriene B4, thromboxane B2 and prostaglandin E2 in rectal dialysates and concentrations of substance P, neurokinin A, somatostatin, vasoactive intestinal polypeptide and calcitonin gene-related peptide in rectal biopsies from 19 patients with active, distally located, ulcerative colitis were measured before and after rectal administration of a 200-mg dose of ropivacaine- or placebo-gel by use of radioimmunoassays. For comparison with normal conditions, concentrations of neuropeptides were measured in another 19 patients with relapsing ulcerative colitis and 14 controls with non-inflamed colon.RESULTS: No significant changes in concentrations of eicosanoids or neuropeptides were observed after ropivacaine or placebo administration. Baseline concentrations of all neuropeptides, except somatostatin, were significantly lower in active ulcerative colitis than in controls with non-inflamed colon.CONCLUSIONS: These findings reveal no evidence of anti-inflammatory actions by ropivacaine in active ulcerative colitis and thus provide no rationale for topical treatment with local anaesthetics.

Published
2002

44. In Response

Author

Mertz-Nielsen, A., primary, Hillingsø, J., additional, Frøkær, H., additional, Bukhave, K., additional, and Rask-Madsen, J., additional

Published
1996
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