THE PHARMACOKINETICS AND PHARMACODYNAMICS OF METHYLPREDNISOLONE IN CHRONIC RENAL FAILURE
作者:
Mark,
Milad Elizabeth,
Ludwig Kim,
Lew Romesh,
Kohli William,
期刊:
American Journal of Therapeutics
(OVID Available online 1994)
卷期:
Volume 1,
issue 1
页码: 49-57
ISSN:1075-2765
年代: 1994
出版商: OVID
关键词: methylprednisolone;pharmacokinetics;pharmacodynamics;cell trafficking;adrenal suppression;immunosuppression;chronic renal failure
数据来源: OVID
摘要:
Methylprednisolone (MP) pharmacokinetics and its directly suppressive effects on cortisol secretion, circulating T-cells, and basophils in blood were compared in six chronic renal failure (CRF) subjects and six healthy controls after an IV administration of MP 0.6 mg kg-1as the sodium succinate ester. The CRF subjects were studied between hemodialysis treatments. The total clearance of methylprednisolone sodium succinate (the prodrug) was reduced by 40% in CRF; however, the pharmacokinetics of methylprednisolone remained unchanged. Methylprednisolone clearance was approximately 280 ml h-1kg-1and volume of distribution was about 1.1 L kg-1. Physiological pharmacodynamic models were applied for the immediate effects of MP, based on the premise that receptor binding is followed by rapid suppression of the secretion of cortisol and recirculation of basophils, T-helper cells, and T-suppressor cells, which persist until inhibitory concentrations (IC50)of methylprednisolone disappear. The difference in (IC50)for each pharmacodynamic parameter was not statistically significant, suggesting no difference in the responsiveness of these factors to methylprednisolone in CRF. As the pharmacokinetics of other corticosteroids are altered in CRF, the lack of pharmacokinetic and pharmacodynamic changes of methylprednisolone may engender a therapeutic advantage for this corticosteroid in CRF.
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