The use of cimetidine as a selective inhibitor of dapsone N-hydroxylation in man

Autor:	Coleman, AK Scott, Alasdair Breckenridge, B.K. Park
Rok vydání:	1990
Předmět:	Pharmacology Adult Male business.industry Drug interaction Dapsone Haemolysis Hydroxylation Pharmacokinetics Histamine H2 receptor Toxicity Medicine Humans Pharmacology (medical) Cimetidine business Methemoglobinemia medicine.drug Antibacterial agent Research Article
Zdroj:	British journal of clinical pharmacology. 30(5)
ISSN:	0306-5251
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da053b3ee1b0e2ec452d13953afe92ce https://pubmed.ncbi.nlm.nih.gov/2271376 Zobrazit plný text záznamu Plný text