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Titolo:
CIMETIDINE IMPROVES THE THERAPEUTIC TOXIC RATIO OF DAPSONE IN PATIENTS ON CHRONIC DAPSONE THERAPY
Autore:
RHODES LE; TINGLE MD; PARK BK; CHU P; VERBOV JL; FRIEDMANN PS;
Indirizzi:
UNIV LIVERPOOL,DEPT DERMATOL,POB 147 LIVERPOOL L69 3BX MERSEYSIDE ENGLAND UNIV LIVERPOOL,DEPT PHARMACOL & THERAPEUT LIVERPOOL L69 3BX MERSEYSIDE ENGLAND ROYAL LIVERPOOL UNIV HOSP,DEPT HAEMATOL LIVERPOOL MERSEYSIDE ENGLAND
Titolo Testata:
British journal of dermatology
fascicolo: 2, volume: 132, anno: 1995,
pagine: 257 - 262
SICI:
0007-0963(1995)132:2<257:CITTTR>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
INDUCED HEMOLYTIC-ANEMIA; N-HYDROXYLATION; DERMATITIS-HERPETIFORMIS; VITAMIN-E; PHARMACOKINETICS; METABOLITES; ACETYLATION; CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
29
Recensione:
Indirizzi per estratti:
Citazione:
L.E. Rhodes et al., "CIMETIDINE IMPROVES THE THERAPEUTIC TOXIC RATIO OF DAPSONE IN PATIENTS ON CHRONIC DAPSONE THERAPY", British journal of dermatology, 132(2), 1995, pp. 257-262

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 ofdapsone. 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 dairy,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 baselineto 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 maybe appropriate for patients who require high-dose dapsone, or those who are particularly susceptible to dapsone-induced haemotoxicity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 03:55:26