Distribution Studies of Salicylazosulfapyridine and its Metabolites

Peppercorn, Mark A.; Goldman, Peter

doi:10.1016/s0016-5085(73)80035-6

Cited by 240 publications

(46 citation statements)

References 5 publications

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“…In urine, total recovery in patients in Group I was 26.5% and was predictably reduced in patients with ileostomy. This result is comparable with those of others (Das et al, 1973;Peppercorn & Goldman, 1973;Schroder & Campbell, 1972). The apparent half-time of 5-ASA, in the patient whose urine was collected in sufficient separate aliquots for the calculation to be made, was 4.4h.…”

Section: -Asasupporting

confidence: 91%

“…5-ASA. Serum 5-ASA concentrations are known to be very low after the oral administration of SASP (Das et al, 1973;Peppercorn & Goldman, 1973) and we did not measure them in the serum.…”

Section: Resultsmentioning

confidence: 99%

“…Sulphapyridine is almost totally absorbed from the colon and metabolized by acetylation, hydroxylation, and glucuronidation. Some of the 5-ASA is absorbed and excreted in the urine, mostly in the acetylated form, but most of the 5-ASA is excreted in the faeces (Schroder & Campbell, 1972;Das et al, 1973;Peppercorn & Goldman, 1973). Our aims in this study were to compare the disposition and metabolism of SASP in patients with and without inflammatory bowel disease and to extend our knowledge of its disposition as well as the disposition of its metabolites by measuring their urinary and biliary clearances and apparent volumes of distribution.…”

Section: Introduction Methodsmentioning

confidence: 99%

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The disposition and metabolism of sulphasalazine (salicylazosulphapyridine) in man.

Azadkhan¹,

Truelove²,

Aronson³

1982

Brit J Clinical Pharma

121

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1 We have investigated the disposition and metabolism of sulphasalazine (SASP) in eight adults with and without inflammatory bowel disease. 2 SASP is poorly absorbed (less than 12%) and the half-time measured in the serum, 10.2 h, is probably the half-time of absorption and therefore an overestimate of the true half-time. The apparent volume of distribution is low (less than 9 l). Renal and biliary clearance rates are low (5.5 and 2.1 ml min-1 respectively) probably due to a high degree of protein binding. Of the absorbed SASP, two thirds is excreted in the urine and one third in the bile. 3 Most of the SASP reaches the colon and is there split by bacteria, forming sulphapyridine (SP) and 5-aminosalicylic acid (5-ASA). 4 SP is almost completely absorbed and, with its metabolites, is excreted in the urine (SP renal clearance rate 32.1 ml min-1). There is no enterohepatic recirculation. 5 Of the 5-ASA released in the colon at least 25% is absorbed and rapidly eliminated in the urine after acetylation. At least 50% is eliminated in the faeces. 6 There are no differences in disposition characteristics when comparing patients with and without inflammatory bowel disease but the metabolism of SASP is markedly reduced in patients taking antibiotics and after removal of the large bowel.

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Section: -Asasupporting

confidence: 91%

“…5-ASA. Serum 5-ASA concentrations are known to be very low after the oral administration of SASP (Das et al, 1973;Peppercorn & Goldman, 1973) and we did not measure them in the serum.…”

Section: Resultsmentioning

confidence: 99%

Section: Introduction Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The disposition and metabolism of sulphasalazine (salicylazosulphapyridine) in man.

Azadkhan¹,

Truelove²,

Aronson³

1982

Brit J Clinical Pharma

121

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“…The most prevalent scenario is that SASP serves as a vehicle to deliver SP and 5-ASA to the colon and cecum in higher concentrations than can be achieved by oral administration of these metabolites alone. 7,8,36,38,39 If these hypotheses are correct, subjects with the ABCG2-A allele are expected to exhibit reduced clinical efficacy owing to lower SASP exposure in the lower intestinal tract (which, in turn, may be associated with lower SP and 5-ASA formations in this tract), despite high plasma concentrations and AUC of SASP. Similar to ulcerative colitis and Crohn's disease, questions still exist as to whether SASP itself or its metabolites, SP and 5-ASA, are responsible for specific antirheumatic effects of SASP; however, there is evidence that SP is also the active moiety of SASP in rheumatoid arthritis.…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenetic Characterization of Sulfasalazine Disposition Based on NAT2 and ABCG2 (BCRP) Gene Polymorphisms in Humans

Yamasaki

Ieiri

Kusuhara

et al. 2008

Clin Pharmacol Ther

147

114

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The role of breast cancer resistance protein (BCRP), an efflux ABC transporter, in the pharmacokinetics of substrate drugs in humans is unknown. We investigated the impact of genetic polymorphisms of ABCG2 (421C>A) and NAT2 on the pharmacokinetics of sulfasalazine (SASP), a dual substrate, in 37 healthy volunteers, taking 2,000 mg of conventional SASP tablets. In ABCG2, SASP AUC(0-48) of C/C, C/A, and A/A subjects was 171 +/- 85, 330 +/- 194, and 592 +/- 275 microg h/ml, respectively, with significant differences among groups. In contrast, AUC(0-48) of sulfapyridine (SP) tended to be lower in subjects with the ABCG2-A allele as homozygosity. In NAT2, AUC(AcSP)/AUC(SP) was significantly higher in rapid than in intermediate and slow acetylator (SA) genotypes. We successfully described the pharmacokinetics of SASP, SP, and N -acetylsulfapyridine (AcSP) simultaneously by nonlinear mixed-effects modeling (NONMEM) analysis with regard to both gene polymorphisms. The data indicate that SASP is a candidate probe of BCRP, particularly in its role in intestinal absorption.

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“…Goldman et al performed studies that compared the effects of germfree and conventional rats on salicylazosulfapyridine (SAS). [6,13] Conventional rats dosed with SAS excreted urine and feces samples containing the SAS metabolites 5-aminosalicylate (5AS) and sulfapyridine (SP). The germfree rat did not originally produce these metabolites.…”

Section: Introductionmentioning

confidence: 99%

Production of human metabolites by gastrointestinal bacteria as a potential source of post‐mortem alteration of antemortem drug/metabolite concentrations

Martindale

Powers

Bell

2014

Drug Testing and Analysis

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Previous studies have demonstrated that bacterial species are capable of transforming complex chemical substances. Several of these species, native to the human gastrointestinal tract, are active in postmortem decomposition. They have potential to cause biotransformations affecting compound-to-metabolite ratios within the human body, especially after death. Investigation of postmortem effects could supply valuable information, especially concerning compound identification and confirmation. The purpose of this research was to investigate the effects of Escherichia coli, Bacteroides fragilis, and Clostridium perfringens on diazepam and flunitrazepam in Reinforced Clostridial Medium, and to compare bacterial biotransformation products to those of human metabolism. A decrease in diazepam concentration between pre- and post-incubation was observed for samples inoculated with Escherichia coli (14.7-20.2%) as well as Bacteroides fragilis (13.9-25.7%); however there was no corresponding increase in concentration for the monitored human metabolites. Flunitrazepam demonstrated a greater concentration loss when incubated with individual bacterial species as well as mixed culture (79.2-100.0%). Samples incubated with Bacteroides fragilis, Clostridium perfringens, and mixed culture resulted in nearly complete conversion of flunitrazepam. Increased 7-aminoflunitrazepam concentrations accounted for the majority of the conversion; however discrepancies in the mass balance of the reaction suggested the possibility of a minor metabolite that was not monitored in the current analysis. These experiments served as a pilot study and proof of concept that can be adapted and applied to a realm of possibilities. Ultimately, this methodology would be ideal to study compounds that are too toxic or lethal for animal and human metabolic investigations.

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Distribution Studies of Salicylazosulfapyridine and its Metabolites

Cited by 240 publications

References 5 publications

The disposition and metabolism of sulphasalazine (salicylazosulphapyridine) in man.

The disposition and metabolism of sulphasalazine (salicylazosulphapyridine) in man.

Pharmacogenetic Characterization of Sulfasalazine Disposition Based on NAT2 and ABCG2 (BCRP) Gene Polymorphisms in Humans

Production of human metabolites by gastrointestinal bacteria as a potential source of post‐mortem alteration of antemortem drug/metabolite concentrations

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