Interactions of Prednisolone and Other Immunosuppressants Used in Dual Treatment of Systemic Lupus Erythematosus in Lymphocyte Proliferation Assays

Abstract

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 whether there 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 (psi) 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 immuno-suppressants 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.

Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases

“…CQ [10 lM inhibited the proliferation of PHA-stimulated T cells and was less potent than azathioprine (Klinefelter and Achurra 1973). The IC 50 for CQ inhibition of T-cell proliferation was found to be 19.50 ± 2.24, which was comparable to tamoxifen but less potent than steroids (Kamal and Jusko 2004). CQ in combination with the immunosuppressants, dehydro-epiandrosterone and 2-chloro-2 0 -deoxyadenosine, showed additivity in suppressing PHA stimulation, in contrast to combinations of some other immunosuppressants which showed synergistic inhibition (Klinefelter and Achurra 1973).…”

Pharmacokinetics of Prednisolone at Steady State in Young Patients With Systemic Lupus Erythematosus on Prednisone Therapy: An Open-Label, Single-Dose Study

“…3 This has made prednisone therapy in SLE problematic, as clinicians avoid high doses and long-term treatment to prevent drug-related toxicity. This is of particular concern when treating cSLE as adverse effects include growth retardation, susceptibility to infections, hypertension, hyperglycemia, hyperlipidemia, osteoporosis, and avascular osteonecrosis 4 . Awareness of these side effects has led to dosing prednisone based on achieving a balance between therapeutic efficacy and toxicity.…”

Studi Retrospektif Penggunaan Obat dan Potensi Interaksi Obat Pasien Systemic Lupus Erythematosus

“…Selain itu agen sitotoksik seperti siklofosfamid dan azaioprin tidak jarang digunakan dalam terapi SLE. Terapi SLE dengan obat-obat tersebut berpotensi menimbulkan adverse drug reaction yang mengakibatkan penurunan kualitas hidup pasien SLE (Kamal & Jusko, 2014). Potensi interaksi obat yang cukup tinggi pada pasien SLE yang menggunakan kortokosteroid dan agen immunosupresan serta obat lain yang mungkin digunakan oleh pasien SLE perlu diwaspadai (Kamal & Jusko, 2014).…”