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 pharmacodynamics 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.
Jusko
W J
WJ
Department of Pharmaceutics, State University of New York at Buffalo 14260, USA.
Milad
M A
MA
Ludwig
E A
EA
Lew
K H
KH
Kohli
R K
RK
D000328:Adult; D001491:Basophils / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008775:Methylprednisolone / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008875:Middle Aged; D006435:Renal Dialysis; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
D006854:Hydrocortisone; D008775:Methylprednisolone