ISSN:
1365-2133
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
We have previously shown that cimetidine, given concurrently for 2 weeks to patients on chronic dapsone therapy, reduced methaemoglobinaemia by inhibiting the formation of the toxic hydro-xylamine metabolite of dapsone. The aim of the present study was to examine the effect of this combination on the benefit/toxic ratio of dapsone over a longer period.Eight patients (six dermatitis herpetiformis, one linear IgA disease, one folliculitis decalvans) on long-term dapsone 50-100 mg daily, took cimetidine 1·6g daily concurrently for 3 months. At 3-weekly intervals, a clinical assessment was made, plasma dapsone and methaemoglobin were measured, and parameters of oxidative haemolysis were monitored. The dapsone level rose from 2298±849 ng/ml (mean+SD) at baseline to 3006±1131 ng/ml at week 3 of cimetidine (P〈0·01). This rise in plasma dapsone was sustained during cimetidine administration, falling to 2446±954 ng/ml when cimetidine was stopped (P〈0·02). The methaemoglobin fell from 5·5·2·2% (mean±SD) at baseline to 3·9±1·1% at week 3 (P〈0·01). and remained low until week 12, when there was a return to baseline values (P〈0·01). The haemoglobin did not change from the baseline of 12·7·0·3 g/dl (mean±SD), and other parameters of haemolysis were unaltered. There was a fall in the visual analogue score for headache (P〈0·05), but this was not associated with any deterioration in control of the skin disorders.Hence, long-term concurrent cimetidine results in increased plasma dapsone levels without increased haemolysis, and is accompanied by reduced methaemoglobinaemia for more than 2 months. Cimetidine thus improves the therapeutic/toxic ratio of dapsone. Such a therapeutic strategy may be appropriate for patients who require high-dose dapsone, or those who are particularly susceptible to dapsone-induced haemotoxicity.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1365-2133.1995.tb05022.x
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