Premium
The use of cimetidine as a selective inhibitor of dapsone N‐ hydroxylation in man.
Author(s) -
Coleman MD,
Scott AK,
Breckenridge AM,
Park BK
Publication year - 1990
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1990.tb03847.x
Subject(s) - cimetidine , dapsone , pharmacology , urine , hydroxylation , medicine , glucuronide , chemistry , immunology , biochemistry , enzyme
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 micrograms ml‐1 h) was significantly increased (P less than 0.001) in the presence of cimetidine (43.3 +/− 8.8 micrograms ml‐1 h). 3. Peak methaemoglobin levels observed after dapsone administration (2.5 +/− 0.6%) were significantly (P less than 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 less than 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.