Abstract

The clinical use of dapsone has expanded over the last decade. Dapsone is now the drug of choice for certain autoimmune-associated disorders such as dermatitis herpetiformis, and is an important component of prophylaxis and chemotherapy for opportunistic infections, such as P. carnii pneumonia, in AIDS patients. In both situations, dapsone's hemotoxicity; viz, methemoglobinemia and hemolytic anemia, are dose limiting in therapy. Over the life of this grant, we have used a rat model to identify the hemotoxic metabolites (N-hydroxydapsone (DDS-NOH) and N-acetyl-N- hydroxydapsone (MADDS-NOH)) of the drug and to gain insight into the mechanism underlying the hemolytic response. We now propose to test the hypothesis that the insight gained with the rat model can be used to reduce the severity of dapsone-induced hemotoxicity in humans and hence, improve the therapeutic ratio of the drug.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR001070-22
Application #
6280110
Study Section
Project Start
1997-12-01
Project End
1998-11-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
22
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Medical University of South Carolina
Department
Type
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425

  Publications

Kelly, Clare B; Hookham, Michelle B; Yu, Jeremy Y et al. (2018) Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes. Diabetes Care 41:120-127
Putterman, Chaim; Pisetsky, David S; Petri, Michelle et al. (2018) The SLE-key test serological signature: new insights into the course of lupus. Rheumatology (Oxford) 57:1632-1640
Hall, Jordan T; Ebeling, Myla; Shary, Judy R et al. (2018) The relationship between physical activity and vitamin D status in postpartum lactating and formula-feeding women. J Steroid Biochem Mol Biol 177:261-265
Kelly, Clare B; Hookham, Michelle B; Yu, Jeremy Y et al. (2018) Response to Comment on Kelly et al. Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes. Diabetes Care 2018;41:120-127. Diabetes Care 41:e102-e103
Bell, Katherine A; Wagner, Carol L; Perng, Wei et al. (2018) Validity of Body Mass Index as a Measure of Adiposity in Infancy. J Pediatr 196:168-174.e1
Sen, Sarbattama; Penfield-Cyr, Annie; Hollis, Bruce W et al. (2017) Maternal Obesity, 25-Hydroxy Vitamin D Concentration, and Bone Density in Breastfeeding Dyads. J Pediatr 187:147-152.e1
Wolf, Bethany J; Spainhour, John C; Arthur, John M et al. (2016) Development of Biomarker Models to Predict Outcomes in Lupus Nephritis. Arthritis Rheumatol 68:1955-63
Wagner, C L; Baggerly, C; McDonnell, S et al. (2016) Post-hoc analysis of vitamin D status and reduced risk of preterm birth in two vitamin D pregnancy cohorts compared with South Carolina March of Dimes 2009-2011 rates. J Steroid Biochem Mol Biol 155:245-51
Hollis, Bruce W; Wagner, Carol L (2016) Response to commentary by D Roth. Evid Based Med 21:120
Hollis, Bruce W; Wagner, Carol L; Howard, Cynthia R et al. (2015) Maternal Versus Infant Vitamin D Supplementation During Lactation: A Randomized Controlled Trial. Pediatrics 136:625-34

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