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Interactions of Prednisolone and Other Immunosuppressants Used in Dual Treatment of Systemic Lupus Erythematosus in Lymphocyte Proliferation Assays
Author(s) -
Kamal Mohamed A.,
Jusko William J.
Publication year - 2004
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270004267808
Subject(s) - prednisolone , medicine , pharmacology , azathioprine , drug , lupus erythematosus , immunology , immunosuppression , disease , antibody
Systemic lupus erythematosus is an autoimmune disease primarily affecting women. Currently systemic lupus erythematosus therapy is suboptimal due to adverse effects of immunosuppressants, particularly corticosteroids. This study determines the single effects of prednisolone, dehydroepiandrosterone, bromocriptine, tamoxifen, mycophenolic acid, 2‐chloro‐2′‐deoxyadenosine, azathioprine, and chloroquine on lectin‐stimulated proliferation of human T lymphocytes, as well as determining whetherthere are interactions in the joint effects of prednisolone and these agents. The T lymphocytes from the whole blood of 10 middle‐aged women were stimulated by phytohemagglutinin and cultured with varying drug concentrations. The Hill function was used to evaluate single‐drug response data. Isobolograms were constructed to qualitatively analyze interactions. Parametric analysis based on competitive and noncompetitive interaction models was further applied to quantify the joint interactions and predict steroid‐sparing potential. The surface interaction parameter (ψ) estimated from parametric analysis was in concordance with isobolographic inspection for all interactions studied. All interactions favored the noncompetitive model. Results suggest that dehydroepiandrosterone is additive in its effect with prednisolone, whereas tamoxifen interacts synergistically, both providing steroid‐sparing effects. Novel immunosuppressants such as mycophenolic acid may still provide added pharmacologic benefit during therapy despite a slight antagonistic interaction with prednisolone. These studies help rationalize actual or potential use of other drugs with prednisolone in the treatment of systemic lupus erythematosus.