Cortisol pharmacodynamic response to long-term methylprednisolone in renal transplant recipients.

摘要: Study Objective. To examine the pharmacodynamic patterns of cortisol and pharmacokinetic values long-term methylprednisolone in renal transplant recipients. Design. Twenty-four-hour evaluation patients who participated a glucocorticoid-monitoring program. Setting. University-based clinic. Patients. Fourteen recipients studied during clinically stable period. Interventions. The daily oral dose for each patient was administered intravenously serial plasma samples were obtained over 24 hours. Measurements Main Results. Methylprednisolone analyzed by high-performance liquid chromatography. baseline morning serum concentrations ranged from 9.8–210.7 ng/ml. After drug administered, declined linear fashion with mean suppression half-life 2.4 ± 0.9 hours. nadir reached at 12–16 hours 11 14 patients. return area under curve (AUC-Cret) noted all 57–987 ng·hr/ml. total greater had been transplanted longer than 2 years (1676 252 vs 836 405 ng·hr/ml; p<0.05) compared more recently clearance 100–1181 ml/hr/kg volume distribution 1.3 0.6 L/kg. 1.2–4.7 correlation between AUC-Cret AUC −0.64 (p<0.05). Conclusions. response may be associated part steroid exposure. However, interrelationship endocrine immune system also affect cortisol's disposition subsequent recovery this population. Considerable interpatient variability apparent both as well pharmacokinetics methylprednisolone. These findings suggest individualized dosing method necessary to optimize immunosuppressive effect glucocorticoids minimize clinical toxicity.