Pharmacokinetic observations on dapsone in dermatitis herpetiformis

Swain, Anne; Ahmad, RA; Rogers, H. J.; Leonard, J.N.; Fry, Lionel

doi:10.1111/j.1365-2133.1983.tb04583.x

Cited by 29 publications

(15 citation statements)

References 12 publications

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“…ment of acetylator phenotype (Adam et al, 1984;Horai et al, 1985;Hutchings et al, 1984). Swain et al (1983) noted that after a single dose of 150 mg no patients or volunteers suffered adverse effects. However, methaemoglobin levels were not determined in these studies.…”

Section: Discussionmentioning

confidence: 99%

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

Coleman¹,

Scott²,

Breckenridge³

et al. 1990

Brit J Clinical Pharma

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1 The N-hydroxylation of dapsone is thought to be responsible for the methaemoglobinaemia and haemolysis associated with this drug. We wished to investigate the effect of concurrent administration of cimetidine (400 mg three times per day) on the disposition of a single dose (100 mg) of dapsone in seven healthy volunteers in order to inhibit selectively N-hydroxylation.2 The AUC of dapsone (31.0 ± 7.2 ,ug ml-' h) was significantly increased (P < 0.001) in the presence of cimetidine (43.3 ± 8.8 ,ug ml-' h).3 Peak methaemoglobin levels observed after dapsone administration (2.5 ± 0.6%) were significantly (P < 0.05) reduced in the presence of cimetidine (0.98 ± 0.35%). 4 The percentage of the dose excreted in urine as the glucuronide of dapsone hydroxylamine was significantly (P < 0.05) reduced in the presence of cimetidine (34.2 ± 9.3 vs 23.1 ± 4.2%). 5 Concurrent cimetidine therapy might reduce some of the haematological side-effects of dapsone.

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Section: Discussionmentioning

confidence: 99%

“…Dapsone is also used as a malarial prophylatic with pyrimethamine (Bruce-Chwatt, 1982). It is effective in the treatment of dermatitis herpetiformis (Swain et al, 1983), Pneumocystis carinii in AIDS patients (Green et al, 1988) and has been used in rheumatoid arthritis (Grindulus & MacConkey, 1984).…”

Section: Introductionmentioning

confidence: 99%

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

Coleman¹,

Scott²,

Breckenridge³

et al. 1990

Brit J Clinical Pharma

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“…It has a relatively long elimination half-life (Ahmad & Rogers, 1980a;Gelber et al, 1971;Lammintausta et al, 1979;Peters et al, 1981;Swain et al, 1983). Enterohepatic circulation occurs (Neuvonen et al, 1980) and the drug is extensively bound to serum proteins (Ahmad & Rogers, 1980a).…”

Section: Introduction Methodsmentioning

confidence: 99%

The pharmacokinetics of dapsone after oral administration to healthy volunteers.

Pieters¹,

Zuidema²

1986

Brit J Clinical Pharma

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After oral administration of 100 mg dapsone (DDS) to 25 healthy volunteers peak serum DDS concentrations between 1.10 and 2.33 mg I-1 were reached within 0.5 to 4 h. AUCs varied from 20.3 to 75.4 mg I -1 h, while the elimination half-lives ranged from 11.5 to 29.2 h. The apparent volumes of distribution were 0.84 to 1.26 1 kg-l body weight, assuming complete bioavailability. Statistically significant differences in peak drug concentration, peak time and AUC existed between males and females. Absorption and elimination of DDS appeared to be faster than reported in other studies, suggesting differences in DDS kinetics between healthy volunteers and patients.

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“…Ellard et al (1974) showed that control of symptoms of patients with dermatitis herpetiformis was not correlated significantly to plasma DDS or MADDS concentrations but adverse effects (methaemoglobinaemia and Heinz-body formation) were correlated significantly to plasma DDS. Swain et al (1983) studied the pharmacokinetics of DDS in patients with dermatitis herpetiformis who needed doses of DDS ranging from 50 mg/week to 700 mg/day to control the rash. Plasma DDS and MADDS were monitored after a single 150 mg oral dose of DDS.…”

Section: Introductionmentioning

confidence: 99%

Agranulocytosis Associated with Maloprim: Review of Cases

1986

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1 Twenty-one cases of agranulocytosis following dosage with one tablet of Maloprim given once or twice weekly are reviewed. 2 Of the 18 individuals for whom the dose is certain 12 were taking twice-weekly Maloprim. Time of onset was 7-9 weeks in 15 of 19 cases where duration of dosage is known. 3 Nine patients died, 12 recovered. Of those who died six were taking Maloprim twice weekly, one once weekly and two at an uncertain dosage. 4 The available data suggest that this is an idiosyncratic reaction to dapsone exacerbated by the concomitant administration of pyrimethamine.

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Pharmacokinetic observations on dapsone in dermatitis herpetiformis

Cited by 29 publications

References 12 publications

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

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

The pharmacokinetics of dapsone after oral administration to healthy volunteers.

Agranulocytosis Associated with Maloprim: Review of Cases

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