Immunosuppressant pharmacodynamics on lymphocytes from healthy subjects and patients with chronic renal failure, nephrosis, and psoriasis: possible implications for individual therapeutic efficacy

Clinical Pharmacology and Therapeutics
T HiranoM Koga

Abstract

In organ transplantation, patients with peripheral blood mononuclear cells (PBMCs) that exhibit resistance to cyclosporine (INN, ciclosporin) or glucocorticoids in vitro are refractory to therapy based on these drugs in vivo. However, detection or distribution of the resistant patients with immunologic disorders remains to be documented. Drug sensitivity tests were performed with PBMCs from four subject groups: 69 healthy subjects, 100 patients with chronic renal failure, 38 patients with nephrosis, and 51 patients with psoriasis. The values for the concentration that produces 50% lymphocyte-mitosis inhibition (IC50) of the drugs on PBMC blastogenesis were estimated, and individual variations or group differences in the IC50 values were examined. The median cyclosporine IC50 values of the four subject groups were similar, but large individual deviations in the IC50 values were observed. Individual differences in prednisolone IC50 values were spread from 1 to 3500 ng/ml. When compared with healthy subjects, a significantly large number of the patients with chronic renal failure group exhibited low responses to prednisolone (p < 0.04). In contrast, no significant difference in the methylprednisolone IC50 was observed among the gr...Continue Reading

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Citations

Apr 12, 2005·Transplant International : Official Journal of the European Society for Organ Transplantation·Kentaro SugiyamaToshihiko Hirano
Oct 25, 2003·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·Salim FredericksIain A M MacPhee
Oct 8, 2009·Clinical Journal of the American Society of Nephrology : CJASN·Brad H RovinDaniel J Birmingham
Sep 29, 2019·Pediatrics International : Official Journal of the Japan Pediatric Society·Wencheng XuToshihiko Hirano
Aug 17, 2000·Clinical Transplantation·T HiranoT Nagao
Sep 28, 2002·International Immunopharmacology·Toshihiko HiranoMasaaki Miyaoka
Dec 13, 2006·International Immunopharmacology·Toshihiko Hirano

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