METHYLPREDNISOLONE PHARMACOKINETICS AND PHARMACODYNAMICS IN CHRONIC-RENAL-FAILURE

Methylprednisolone (MP) pharmacokinetics and its directly suppressive effects on cortisol secretion and cell trafficking were compared in 6 chronic renal failure (CRF) subjects and 6 healthy controls. After IV administration of MP 0.6 mg/kg as Solu-Medrol, the pharmacokinetics of methylprednisolone were similar. The clearance was about 280 ml/hr/kg , volume of distribution was 1.1 1/kg, t1/2 was 2.7 hr, and fraction u nbound was 0.2. Physiologic pharmacodynamic models were applied for th e suppression of cortisol secretion and recirculation of basophils, T- helper cells, and T-suppressor cells. The net response (area under the curve) and inhibitory concentrations (IC50) of methylprednisolone for each pharmacodynamic parameter were similar in both groups. As the ph armacokinetics of other corticosteroids are altered in CRF, the lack o f pharmacokinetic/dynamic changes of methylprednisolone may offer a th erapeutic advantage for CRF patients.