The use of cimetidine as a selective inhibitor of dapsone N‐ hydroxylation in man.

Coleman,; Scott, AK; Breckenridge, AM; Park, BK

doi:10.1111/j.1365-2125.1990.tb03847.x

Cited by 88 publications

(41 citation statements)

References 23 publications

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“…This metabolite is formed due to the N-hydroxylation of dapsone by multiple hepatic cytochrome P450 isozymes, including CYP3A4 [23][24][25][26] . Cimetidine, a histamine H 2 receptor antagonist, can reduce the N-hydroxylation of dapsone [31] . This reduction was demonstrated to result in more than a 25% decrease in methemoglobinemia in patients who received dapsone for the treatment of dermatitis herpetiformis [32] .…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Dapsone in the Treatment of Pemphigus Vulgaris: A Single-Center Case Study

Baum¹,

Debby²,

Gilboa³

et al. 2016

Dermatology

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Background: Pemphigus vulgaris (PV) is a chronic autoimmune blistering disease. Most patients require long-term therapy with systemic steroids, and a steroid-sparing agent is usually also utilized. Dapsone is a chemotherapeutic agent with anti-inflammatory properties that is used as a steroid-sparing agent in PV. Objective: The aim of the present study was to evaluate the efficacy of dapsone as an adjuvant therapy in patients with PV. Methods: A retrospective analysis of patients' files was performed. All 26 patients included in the study group were treated with dapsone as an adjuvant to systemic steroids for at least 3 consecutive months and were followed up during their dapsone treatment period. Results: After 3 months of treatment with dapsone, 13 patients were in the consolidation phase, 4 patients demonstrated partial remission on minimal therapy, 7 patients demonstrated complete remission on minimal therapy, and 2 patients were defined as treatment failures. The trend of clinical improvement continued after 6 months of treatment and at the study end point. Conclusion: This retrospective case series, one of the largest reported, indicates that dapsone is efficacious and safe for patients with PV in whom it is well tolerated soon after the initiation of treatment.

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Section: Discussionmentioning

confidence: 99%

Efficacy of Dapsone in the Treatment of Pemphigus Vulgaris: A Single-Center Case Study

Baum¹,

Debby²,

Gilboa³

et al. 2016

Dermatology

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“…Since losartan has been shown to be extensively metabolized in human liver slice incubations [22], the most likely explanation for the decrease in losartan AUC is inhibition of one or more cytochrome P450 pathways for metabolism of losartan, (presumably CYPs 3A4 and 2C9 [6]). Cimetidine has been shown to alter the metabolism of other drugs which are metabolized by CYP 3A4, including dihydropyridine calcium channel blockers [7,8,9], dapsone [10], and midazolam [7]. Other mechanisms may apply including inhibition of renal tubular secretion of losartan, although the minor role of the renal route in the elimination of losartan (only 3% of an oral dose of losartan is excreted unchanged in the urine in patients with normal renal function [23]) suggests that this is unlikely.…”

Section: Discussionmentioning

confidence: 99%

“…While losartan is not a prodrug, formation of the metabolite is important to the activity of losartan as a once-daily treatment of hypertension [5]. Available in vitro data suggest that this reaction can be catalysed by CYPs 3A4 and 2C9 [6].Numerous studies have shown that cimetidine, a commonly prescribed H2-antagonist, nonspecifically inhibits the oxidative metabolism of many drugs, including those metabolized by CYP 3A4 such as nifedipine, nisoldipine and dapsone [7][8][9][10]. Since the duration of action of losartan is dependent on the formation of E-3174, it was of interest to determine whether cimetidine alters concentrations in plasma of losartan and/or E-3174.…”

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confidence: 99%

Effects of cimetidine on pharmacokinetics and pharmacodynamics of losartan, an AT1-selective non-peptide angiotensin II receptor antagonist

Goldberg

Bradstreet

et al. 1995

Eur J Clin Pharmacol

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This was a 2-period randomized, crossover study in 8 healthy males to determine the effects of cimetidine (400 mg q.i.d. for 6 days) on the pharmacokinetics and pharmacodynamic effects of the angiotensin II receptor antagonist, losartan (100 mg). Cimetidine increased the AUC for losartan 18% without affecting the AUC for E-3174, the active metabolite of losartan. The increase in plasma renin activity following losartan was not affected by cimetidine (maximum mean increases 12.6 and 12.1 ng Ang I.ml-1.h-1 without and with cimetidine, respectively). These results indicate that cimetidine does not appear to alter the pharmacokinetics or pharmacodynamics of losartan to a clinically significant extent.

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“…Unfortunately the applications of dapsone are dose-limited due to its hepatic phase I activation to haemotologically toxic hydroxylamines [12,13].…”

Section: -Aminodiphenyl Sulphones and Especially 44mentioning

confidence: 99%

Quantitative Structure–Activity and Structure–Toxicity Relationships of 4‐Aminodiphenyl Sulphone Derivatives with Antiinflammatory Activity

Seydel¹,

Bürger

Saxena

et al. 1999

Quant. Struct.‐Act. Relat.

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It has been shown that dapsone and its derivatives are not only potential inhibitors of bacterial and plasmodial folate synthesis but also possess antiin¯ammatory activity. The application of dapsone is, however, limited by its toxic side effects at higher dose manifested especially by its potential to produce methaemoglobin. We have analyzed the structural dependence of this property on a set of 29 derivatives. A highly signi®cant nonlinear dependence on the lipophilicity could be derived. Two exceptions to the general relation were found and the mechanism for these could be derived. It was also shown that the bilinear dependence is not due to lipophilicity mediated diffusion into erythrocytes. It was found that the diffusion is linearly dependent on lipophilicity. Principal Component (PC)-Analysis revealed that the antiin¯ammatory activities, determined as inhibition of zymosane stimulated cell burst and cell adhesion are orthogonal to methaemoglobin formation and cell death potential of the studied derivatives. The antiin¯ammatory activity seems to depend on electronic and steric effects of the 2 H -substituents. The orthogonality of substituent in¯uences on the toxic and wanted effects opens up the possibility to further optimize the selectivity of aminodiphenylsulphones.

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The use of cimetidine as a selective inhibitor of dapsone N‐ hydroxylation in man.

Cited by 88 publications

References 23 publications

Efficacy of Dapsone in the Treatment of Pemphigus Vulgaris: A Single-Center Case Study

Efficacy of Dapsone in the Treatment of Pemphigus Vulgaris: A Single-Center Case Study

Effects of cimetidine on pharmacokinetics and pharmacodynamics of losartan, an AT1-selective non-peptide angiotensin II receptor antagonist

Quantitative Structure–Activity and Structure–Toxicity Relationships of 4‐Aminodiphenyl Sulphone Derivatives with Antiinflammatory Activity

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