Relationship between high incidence of adverse dapsone reactions and slow acetylate phenotype or low plasma/lymphocyte glutathione level.
OBJECTIVE
To investigate the relationship between high incidence of adverse dapsone reactions in acquired immunodeficiency syndrome (AIDS) patients and slow acetylate phenotype or low plasma/lymphocyte glutathione level of these patients.


METHODS
Twenty-one cases of advanced AIDS patients (CD4 < 200/microliter) were involved in this study, all Europeans except one black, were acetylate phenotyped via analysis of caffeine metabolites, named 5-Acetylamino-6-formylamino-3-methyluracil, 1-Methylxanthine and 5-Acetylamino-6-amino-3-methyluracil, in human urine collected 2 hours after a cup of caffeine-spiked coffee and their plasma/lymphocyte glutathione concentrations were determined, by high performance liquid chromatographic method.


RESULTS
Of the 21 AIDS patients, 15 are slow acetylators, accounting for 74.8%. One of 6 rapid acetylators has adverse dapsone reactions, acounting for 17%, compared with 46% for slow acetylators (7/15). The concentrations of glutathione in plasma/lymphocyte (6.97 +/- 0.95 mumol and 28.75 +/- 2.78 nmol/mg protein) in AIDS patients with adverse dapsone reactions are significantly lower than those (10.90 +/- 1.45 mumol and 32.15 +/- 2.21 nmol/mg protein) of AIDS patients without adverse dapsone reactions, and also than those (11.85 +/- 1.83 mumol and 33.76 +/- 2.32 nmol/mg protein) of health controls.


CONCLUSIONS
Slow acetylators, which lead to accumulation of toxic dapsone metabolites and those subjects who are lower in glutathione level in plasma/lymphocyte because of certain kind of diseases as advanced AIDS are risk population of adverse dapsone reactions. Routinely determining human acetylate phenotype status might be helpful in adjusting and modifying dapsone dosage regimen.
Guo
R
R
Hospital Affiliated to Shandong Medical University, Jinan.
Thormann
W
W
Lauterberg
B
B
D000107:Acetylation; D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism*; D000328:Adult; D000890:Anti-Infective Agents / Q000378:metabolism*; D002110:Caffeine / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003622:Dapsone / Q000009:adverse effects / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000097:blood*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010641:Phenotype
D000890:Anti-Infective Agents; D002110:Caffeine; D003622:Dapsone; D005978:Glutathione