Nephrotoxicity and Molecular Structure

Calder, I. C.; Williams, PJ; Woods, R.; Funder, C. C.; Green, C. R.; Ham, Kathryn N.; Tange, J. D.

doi:10.3109/00498257509052064

Cited by 35 publications

(8 citation statements)

References 6 publications

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“…Less than 2% of the dose was found in faeces also as ac-5-ASA (Table 1). No side effects were observed and all biochemical tests showed normal results, particularly those involving renal function (Calder et al, 1975).…”

Section: Methodsmentioning

confidence: 86%

Kinetics of 5‐aminosalicylic acid after jejunal instillation in man.

Nielsen¹,

Bondesen²

1983

Brit J Clinical Pharma

126

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The human pharmacokinetics of 5‐aminosalicylic acid (5‐ASA), the active moiety of salazosulphapyridine (SASP), is only known from studies in which rapid absorption has been deliberately avoided. The present investigation demonstrates that pure 5‐ASA is absorbed extremely quickly when given as an instillation in the proximal part of the small bowel, and acetylation follows immediately. The metabolite is excreted very rapidly by the liver in small amounts, while the major part is eliminated renally.

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Section: Methodsmentioning

confidence: 86%

Kinetics of 5‐aminosalicylic acid after jejunal instillation in man.

Nielsen¹,

Bondesen²

1983

Brit J Clinical Pharma

126

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“…There is significant delayed absorption in patients with proximal Crohn's disease compared to normal volunteers, and with continued treatment in one patient, absorption returned towards normal. The worry remains that renal toxicity may be a limiting factor of this form of therapy (6)(7)(8)(9). Close monicoring of renal function is an absolute necessity, particularly where long, continued use is contemplated.…”

Section: Discussionmentioning

confidence: 99%

“…It was, therefore, hypothesized that a 5-ASA liquid enema preparation may be suitable for the upper small bowel. The major concern would be increased intestinal absorption and possible renal damage (6)(7)(8). Since the introduction of5-ASA in tablet form, there have been occasional reports of altered serum…”

mentioning

confidence: 99%

Pharmacokinetics of 5-Aminosalicylic Acid Enteral Suspension in Crohn's Disease Patients and Normal Volunteers

Williams¹,

Morgan²

1990

Canadian Journal of Gastroenterology

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5-Aminosalicylic acid (5-ASA) is available in many countries in tablet, enema and suppository form. A new enteral suspension was studied in six patients with Crohn's disease affecting the upper gastrointestinal tract and in six healthy volunteers. Four grams of 5-ASA dissolved in 240 ml suspension was given via a nasoduodenal tube over 4 h. Blood was drawn at 0, l, 2, 3, 4, 5, 6, 7, 8, 12 and 24 h, and 24 h urine and stool were collected for 5-ASA and n-acetyl-5-ASA analyses. All patients and subjects tolerated the procedure without problems and no side effects were encountered. All subjects and volunteers had normal renal function before and after the study; serum creatinine and blood urea nitrogen did not change. Urine recovery of 5-ASA ranged from 0.6 to 3.4 g (controls) and 0.46 to 3.6 g (patients). Stool recovery of 5-ASA was 0.1 to 0.3 g (controls) and 0.12 to 0.54 g (patients). There was delayed absorption of 5-ASA in patients compared to controls, shown by time to peak concentrations (4 to 6 h versus 3 h). Predominantly urine excretion of the n-acetyl metabolite occurred in both groups, with less than 12% stool excretion. Continued treatment induced remission. An enteral suspension of 5-ASA may be of benefit in selected patients with proximal small bowel Crohn's disease.

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“…With increasing awareness of this concept, and so with more information derived from experiments specifically designed to this end, it may be that the scope of such drugs will be found to be remarkably wide. On the one hand there is evidence [39] that the toxicity of certain nephrotoxic analgesic substances appears to be related to their oxidationreduction potentials. Similarly the relative efficacy of various gold salts, used in the treatment of rheumatoid arthritis, might be attributable to their redox potential, but this remains to be established.…”

Section: Resultsmentioning

confidence: 99%