Abstract
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.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Coleman M. D., Hoaksey P. E., Breckenridge A. M., Park B. K. Inhibition of dapsone-induced methaemoglobinaemia in the rat isolated perfused liver. J Pharm Pharmacol. 1990 May;42(5):302–307. doi: 10.1111/j.2042-7158.1990.tb05416.x. [DOI] [PubMed] [Google Scholar]
- Coleman M. D., Russell R. M., Tingle M. D., Park B. K. Inhibition of dapsone-induced methaemoglobinaemia by cimetidine in the presence of trimethoprim in the rat. J Pharm Pharmacol. 1992 Feb;44(2):114–118. doi: 10.1111/j.2042-7158.1992.tb03573.x. [DOI] [PubMed] [Google Scholar]
- Coleman M. D., Scott A. K., Breckenridge A. M., Park B. K. The use of cimetidine as a selective inhibitor of dapsone N-hydroxylation in man. Br J Clin Pharmacol. 1990 Nov;30(5):761–767. doi: 10.1111/j.1365-2125.1990.tb03847.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Coleman M. D., Tingle M. D., Park B. K. Inhibition of dapsone-induced methaemoglobinaemia by cimetidine in the rat during chronic dapsone administration. J Pharm Pharmacol. 1991 Mar;43(3):186–190. doi: 10.1111/j.2042-7158.1991.tb06663.x. [DOI] [PubMed] [Google Scholar]
- Coleman M. D., Winn M. J., Breckenridge A. M., Park B. K. Inhibition of dapsone-induced methaemoglobinaemia in the rat. Biochem Pharmacol. 1990 Feb 15;39(4):802–805. doi: 10.1016/0006-2952(90)90164-g. [DOI] [PubMed] [Google Scholar]
- Cucinell S. A., Israili Z. H., Dayton P. G. Microsomal N-oxidation of dapson as a cause of methemoglobin formation in human red cells. Am J Trop Med Hyg. 1972 May;21(3):322–331. doi: 10.4269/ajtmh.1972.21.322. [DOI] [PubMed] [Google Scholar]
- Degowin R. L., Eppes R. B., Powell R. D., Carson P. E. The haemolytic effects of diaphenylsulfone (DDS) in normal subjects and in those with glucose-6-phosphate-dehydrogenase deficiency. Bull World Health Organ. 1966;35(2):165–179. [PMC free article] [PubMed] [Google Scholar]
- Ellard G. A. Absorption, metabolism and excretion of di(rho-aminophenyl) sulphone (dapsone) and di(rho-aminophenyl) sulphoxide in man. Br J Pharmacol Chemother. 1966 Jan;26(1):212–217. doi: 10.1111/j.1476-5381.1966.tb01823.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ganer A., Knobel B., Fryd C. H., Rachmilewitz E. A. Dapsone-induced methemoglobinemia and hemolysis in the presence of familial hemoglobinopathy Hasharon and familial methemoglobin reductase deficiency. Isr J Med Sci. 1981 Aug;17(8):703–704. [PubMed] [Google Scholar]
- Gelber R., Peters J. H., Gordon G. R., Glazko A. J., Levy L. The polymorphic acetylation of dapsone in man. Clin Pharmacol Ther. 1971 Mar-Apr;12(2):225–238. doi: 10.1002/cpt1971122part1225. [DOI] [PubMed] [Google Scholar]
- Graham W. R., Jr Adverse effects of dapsone. Int J Dermatol. 1975 Sep;14(7):494–500. doi: 10.1111/j.1365-4362.1975.tb04283.x. [DOI] [PubMed] [Google Scholar]
- Grindulis K. A., McConkey B. Rheumatoid arthritis: the effects of treatment with dapsone on hemoglobin. J Rheumatol. 1984 Dec;11(6):776–778. [PubMed] [Google Scholar]
- Grossman S. J., Jollow D. J. Role of dapsone hydroxylamine in dapsone-induced hemolytic anemia. J Pharmacol Exp Ther. 1988 Jan;244(1):118–125. [PubMed] [Google Scholar]
- Harrison J. H., Jr, Jollow D. J. Role of aniline metabolites in aniline-induced hemolytic anemia. J Pharmacol Exp Ther. 1986 Sep;238(3):1045–1054. [PubMed] [Google Scholar]
- Herve P., Tamayo E., Lenys R., Peters A., Rozenbaum A., Floris R. L. Kinetics of CFU-c population after autologous bone marrow graft. Br J Haematol. 1979 Dec;43(4):681–682. doi: 10.1111/j.1365-2141.1979.tb03803.x. [DOI] [PubMed] [Google Scholar]
- Hörnsten P., Keisu M., Wiholm B. E. The incidence of agranulocytosis during treatment of dermatitis herpetiformis with dapsone as reported in Sweden, 1972 through 1988. Arch Dermatol. 1990 Jul;126(7):919–922. doi: 10.1001/archderm.1990.01670310081011. [DOI] [PubMed] [Google Scholar]
- Israili Z. H., Cucinell S. A., Vaught J., Davis E., Lesser J. M., Dayton P. G. Studies of the metabolism of dapsone in man and experimental animals: formation of N-hydroxy metabolites. J Pharmacol Exp Ther. 1973 Oct;187(1):138–151. [PubMed] [Google Scholar]
- Knodell R. G., Browne D. G., Gwozdz G. P., Brian W. R., Guengerich F. P. Differential inhibition of individual human liver cytochromes P-450 by cimetidine. Gastroenterology. 1991 Dec;101(6):1680–1691. doi: 10.1016/0016-5085(91)90408-d. [DOI] [PubMed] [Google Scholar]
- Kramer P. A., Glader B. E., Li T. K. Mechanism of methemoglobin formation by diphenylsulfones. Effect of 4-amino-4'-hydroxyaminodiphenylsulfone and other p-substituted derivatives. Biochem Pharmacol. 1972 May 1;21(9):1265–1274. doi: 10.1016/0006-2952(72)90288-2. [DOI] [PubMed] [Google Scholar]
- Lee B. L., Medina I., Benowitz N. L., Jacob P., 3rd, Wofsy C. B., Mills J., 5th Dapsone, trimethoprim, and sulfamethoxazole plasma levels during treatment of Pneumocystis pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Evidence of drug interactions. Ann Intern Med. 1989 Apr 15;110(8):606–611. doi: 10.7326/0003-4819-110-8-606. [DOI] [PubMed] [Google Scholar]
- Manfredi G., De Panfilis G., Zampetti M., Allegra F. Studies on dapsone induced haemolytic anaemia. I. Methaemoglobin production and G-6-PD activity in correlation with dapsone dosage. Br J Dermatol. 1979 Apr;100(4):427–432. doi: 10.1111/j.1365-2133.1979.tb01644.x. [DOI] [PubMed] [Google Scholar]
- Martin J., Roenigk H. H., Lynch W., Tingwald F. R. Relapsing polychondritis treated with dapsone. Arch Dermatol. 1976 Sep;112(9):1272–1274. [PubMed] [Google Scholar]
- May D. G., Porter J. A., Uetrecht J. P., Wilkinson G. R., Branch R. A. The contribution of N-hydroxylation and acetylation to dapsone pharmacokinetics in normal subjects. Clin Pharmacol Ther. 1990 Dec;48(6):619–627. doi: 10.1038/clpt.1990.204. [DOI] [PubMed] [Google Scholar]
- Ognibene A. J. Agranulocytosis due to dapsone. Ann Intern Med. 1970 Apr;72(4):521–524. doi: 10.7326/0003-4819-72-4-521. [DOI] [PubMed] [Google Scholar]
- Person J. R., Rogers R. S., 3rd Bullous pemphigoid responding to sulfapyridine and the sulfones. Arch Dermatol. 1977 May;113(5):610–615. [PubMed] [Google Scholar]
- Poulsen A., Hultberg B., Thomsen K., Wantzin G. L. Regression of Kaposi's sarcoma in AIDS after treatment with dapsone. Lancet. 1984 Mar 10;1(8376):560–560. doi: 10.1016/s0140-6736(84)90949-8. [DOI] [PubMed] [Google Scholar]
- Swain A. F., Ahmad R. A., Rogers H. J., Leonard J. N., Fry L. Pharmacokinetic observations on dapsone in dermatitis herpetiformis. Br J Dermatol. 1983 Jan;108(1):91–98. doi: 10.1111/j.1365-2133.1983.tb04583.x. [DOI] [PubMed] [Google Scholar]
- Thompson D. M., Main R. A., Beck J. S., Albert-Recht F. Studies on a patient with leucocytoclastic vasculities 'pyoderma gangrenosum' and paraproteinaemia. Br J Dermatol. 1973 Feb;88(2):117–125. [PubMed] [Google Scholar]
- Tingle M. D., Coleman M. D., Park B. K. An investigation of the role of metabolism in dapsone-induced methaemoglobinaemia using a two compartment in vitro test system. Br J Clin Pharmacol. 1990 Dec;30(6):829–838. doi: 10.1111/j.1365-2125.1990.tb05448.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Uetrecht J., Zahid N., Shear N. H., Biggar W. D. Metabolism of dapsone to a hydroxylamine by human neutrophils and mononuclear cells. J Pharmacol Exp Ther. 1988 Apr;245(1):274–279. [PubMed] [Google Scholar]
- Wright J. T., Jr, Goodman R. P., Bethel A. M., Lambert C. M. Cimetidine and dapsone acetylation. Drug Metab Dispos. 1984 Nov-Dec;12(6):782–783. [PubMed] [Google Scholar]
- Zuidema J., Hilbers-Modderman E. S., Merkus F. W. Clinical pharmacokinetics of dapsone. Clin Pharmacokinet. 1986 Jul-Aug;11(4):299–315. doi: 10.2165/00003088-198611040-00003. [DOI] [PubMed] [Google Scholar]