title: Cimetidine improves the therapeutic/toxic ratio of dapsone in patients on chronic dapsone therapy.
abstract: 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 hydroxylamine 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 1.6 g 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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Dermatology, University of Liverpool, U.K.
authors.forename: L E
authors.initials: LE
authors.lastname: Rhodes
authors.forename: M D
authors.initials: MD
authors.lastname: Tingle
authors.forename: B K
authors.initials: BK
authors.lastname: Park
authors.forename: P
authors.initials: P
authors.lastname: Chu
authors.forename: J L
authors.initials: JL
authors.lastname: Verbov
authors.forename: P S
authors.initials: PS
authors.lastname: Friedmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002927:Cimetidine / Q000627:therapeutic use*; D003622:Dapsone / Q000009:adverse effects* / Q000627:therapeutic use; D003874:Dermatitis Herpetiformis / Q000097:blood / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005260:Female; D006261:Headache / Q000139:chemically induced / Q000517:prevention & control; D006461:Hemolysis; D006801:Humans; D008297:Male; D008706:Methemoglobin / Q000032:analysis; D008875:Middle Aged; D010147:Pain Measurement
chemical_list: D002927:Cimetidine; D003622:Dapsone; D008706:Methemoglobin