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 l/kg, t1/2 was 2.7 hr, and fraction unbound was 0.2. Physiologic pharmacodynamic models were applied for the 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 pharmacokinetics of other corticosteroids are altered in CRF, the lack of pharmacokinetic/dynamic changes of methylprednisolone may offer a therapeutic advantage for CRF patients.