Steroid dose sparing: Pharmacodynamic responses to single versus divided doses of methylprednisolone in man

摘要: Inhibitory drug interactions affecting the metabolism of methylprednisolone (MP) may produce either steroid sparing or adverse effects partly by increasing exposure time to steroid. This phenomenon can be mimicked administering MP in divided doses. Two types responses were compared after a single dose (40 mg bolus) and regimen (20 bolus 5 8 hours later) six healthy male volunteers. The suppression basophils measured as whole blood histamine plasma cortisol concentrations was assessed during 32 hours. 37.5% reduction produced 23% overall decreased response. A pharmacodynamic model for basophil cell distribution from an extravascular compartment describes both regimens. slower initial decline related incomplete return blood. 50% inhibitory about ng/ml similar between treatments with continuing 24 values adrenal 1 ng/ml. Pharmacodynamic modeling is useful quantitating corticosteroid generally predicted "dose-sparing" that achieved prolonging concentrations. study supports previous clinical observations patients require morning through evening optimize efficacy while being minimized.