DISPOSITION OF SYNTHETIC GLUCOCORTICOIDS .1. PHARMACOKINETICS OF DEXAMETHASONE IN HEALTHY-ADULTS

被引:103
作者
TSUEI, SE
MOORE, RG
ASHLEY, JJ
MCBRIDE, WG
机构
[1] UNIV SYDNEY,DEPT PHARM,SYDNEY 2006,NEW S WALES,AUSTRALIA
[2] WOMENS HOSP,FOETAL PHARMACOL LAB,FDN 41,SYDNEY 2010,NEW S WALES,AUSTRALIA
来源
JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS | 1979年 / 7卷 / 03期
关键词
dexamethasone; high-performance liquid chromatography; pharmacokinetics; renal excretion;
D O I
10.1007/BF01060016
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The pharmacokinetics of dexamethasone alcohol is described in six male and six female healthy adult volunteers who each received 8 mg of dexamethasone phosphate by bolus intravenous injection. Quantitation of the alcohol was done using a high-performance liquid Chromatographic method with improved specificity. Statistical evaluation of the results generated by nonlinear least-squares regression analysis of the plasma concentration-time data shows that the phosphate ester is very rapidly hydrolyzed to the alcohol and a biexponential equation is the simplest poly exponential equation that is consistent with the data. The terminal phase half-life t1/2β was significantly greater (p<0.05) in males (mean 201.5 min) than in females (mean 142.3 min). The prolonged t1/2β in males did not appear to be caused by an impaired capacity to eliminate dexamethasone since the total plasma clearance did not differ between males (mean 247.5ml/min) and females (mean 242.9 ml/min). There was, however, a high positive correlation between t1/2β and {Mathematical expression} among the 12 adults (r=0.92, p<0.001). There were also significant correlations between {Mathematical expression} and body weight (r=0.67, p<0.05) and t1/2β (r=0.80, p<0.01). The difference in body weight between the sexes seems to be the main factor contributing to the difference observed int1/2β. An average of only 2.6% of the dose was found unchanged in a 24-hr urine sample, and hence it appears that dexamethasone is primarily eliminated by extrarenal, probably hepatic, mechanisms. © 1979 Plenum Publishing Corporation.
引用
收藏
页码:249 / 264
页数:16
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