The use of cimetidine to reduce dapsone-dependent methaemoglobinaemia in dermatitis herpetiformis patients.
1. We have attempted to reduce dapsone-dependent methaemoglobinaemia formation in six dermatitis herpetiformis patients stabilised on dapsone by the co-administration of cimetidine. 2. In comparison with control, i.e. dapsone alone, methaemoglobinaemia due to dapsone fell by 27.3 +/- 6.7% and 26.6 +/- 5.6% the first and second weeks after commencement of cimetidine administration. The normally cyanotic appearance of the patient on the highest dose of dapsone (350 mg day-1), underwent marked improvement. 3. There was a significant increase in the trough plasma concentration of dapsone (2.8 +/- 0.8 x 10(-5)% dose ml-1) at day 21 in the presence of cimetidine compared with control (day 7, 1.9 +/- 0.6 x 10(-5)% dose ml-1, P less than 0.01). During the period of the study, dapsone-mediated control of the dermatitis herpetiformis in all six patients was unchanged. 4. Trough plasma concentrations of monoacetyl dapsone were significantly increased (P less than 0.05) at day 21 (1.9 +/- 1.0 x 10(-5)% dose ml-1) compared with day 7 (1.6 +/- 0.9 x 10(-5)% dose ml-1:control). 5. Over a 12 h period, 20.6 +/- 8.9% (day 0) of a dose of dapsone was detectable in urine as dapsone hydroxylamine. Significantly less dapsone hydroxylamine was recovered from urine at day 14 (15.0 +/- 8.4) in the presence of cimetidine, compared with day 0 (control: P less than 0.05). 6. The co-administration of cimetidine may be of value in increasing patient tolerance to dapsone, a widely used, effective, but comparatively toxic drug.
Coleman
M D
MD
Department of Pharmacology and Therapeutics, Liverpool.
Rhodes
L E
LE
Scott
A K
AK
Verbov
J L
JL
Friedmann
P S
PS
Breckenridge
A M
AM
Park
B K
BK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002927:Cimetidine / Q000494:pharmacology / Q000627:therapeutic use*; D003622:Dapsone / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D003874:Dermatitis Herpetiformis / Q000150:complications / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D008297:Male; D008708:Methemoglobinemia / Q000139:chemically induced* / Q000188:drug therapy; D008875:Middle Aged
D002927:Cimetidine; D003622:Dapsone; C018965:monoacetyldapsone