PHARMACOKINETICS AND PHARMACODYNAMICS OF METHYLPREDNISOLONE IN OBESITY

被引:59
作者
DUNN, TE
LUDWIG, EA
SLAUGHTER, RL
CAMARA, DS
JUSKO, WJ
机构
[1] SUNY BUFFALO,SCH PHARM,DEPT PHARMACEUT,565 HOCHSTETTER HALL,BUFFALO,NY 14260
[2] SUNY BUFFALO,SCH PHARM,DEPT PHARM,BUFFALO,NY 14260
[3] SUNY BUFFALO,SCH MED,DEPT MED,BUFFALO,NY 14214
[4] BUFFALO GEN HOSP,DIV GASTROENTEROL,BUFFALO,NY 14203
[5] BUFFALO GEN HOSP,DEPT PHARM,BUFFALO,NY 14203
关键词
D O I
10.1038/clpt.1991.64
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Methylprednisolone pharmacokinetics and its directly suppressive effects on plasma cortisol, blood histamine (basophils), and circulating helper T cells were evaluated in six obese (at least 35% above ideal body weight) men and six nonobese male volunteers. Methylprednisolone doses of 0.6 mg/kg total body weight were administered as the 21-succinate sodium salt. Absolute clearance (in liters per hour) of methylprednisolone was 40% less in the obese subjects. Total volume of distribution (V(ss)) of methylprednisolone was unchanged (about 120 L), but when normalized for total body weight, V(SS) per kilogram was less in obesity. The patterns of cortisol, blood histamine, and helper T cell responses after methylprednisolone administration were similar in both groups, but more profound effects were observed in the obese subjects. Pharmacodynamic models were applied for these immediate effects of methylprednisolone based on the premise that receptor interactions of steroids are followed by rapid suppression of the circadian rhythm of cortisol and recirculation of basophils and helper T cells, which persist until inhibitory concentrations (IC50) of methylprednisolone disappear. Similar IC50 values for the three effects were obtained in both groups, indicating no intrinsic pharmacodynamic differences in sensitivity to these methylprednisolone effects in obesity. However, methylprednisolone should be administered on the basis of ideal body weight, and the dosing interval should be potentially lengthened because of decreased methylprednisolone clearance in obesity.
引用
收藏
页码:536 / 549
页数:14
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