Immunohematotoxicity studies with combinations of dapsone and zidovudine

We investigated the immunohematoxicities of the antiparasitic drug dapsone (DDS) and the antiretroviral drug zidovudine (ZDV, AZT) given alone or in c ombination in BALB/c mice. DDS is used for prophylaxis and treatment of Pne umocystis carinii infection in AIDS patients. We examined the impact of con current administration of these drugs on the immune and hematopoietic syste ms because DDS causes hematotoxicity and ZDV therapy results in bone marrow toxicity. Daily oral administration of DDS at 25 and 50 mg/kg for 28 days caused a slight anemia, marked methemoglobinemia, reticulocytosis, and a mo derate leukopenia (P < 0.01 for all parameters) but had no discernible effe ct on platelet count. In DDS-treated mice, the proliferative response of sp lenic T cells to concanavalin A was greater than or equal to 35% higher tha n that manifested by splenocytes from vehicle-treated control mice. ZDV at 240 and 480 mg/kg was not immunosuppressive but caused low-grade macrocytic anemia, thrombocytosis, and neutropenia; these effects were drug dose-depe ndent and statistically significant (P < 0.01). Concurrent administration o f DDS and ZDV augmented the severity of ZDV-mediated macrocytic anemia, and 7 of 12 (58%) mice did not survive treatment with the high doses of DDS an d ZDV (50 and 480 mg/kg, respectively). On the other hand, co-administratio n of ZDV mitigated DDS-induced methemoglobinemia and the DDS-associated ele vation in lymphoproliferative response. These data suggest interaction betw een DDS and ZDV in mice and indicate a need for caution in using DDS as lon g-term therapy in AIDS patients receiving ZDV. (C) 2001 Elsevier Science B. V. All rights reserved.