DISPOSITION AND COVALENT BINDING OF IBUPROFEN AND ITS ACYL GLUCURONIDE IN THE ELDERLY

被引:51
作者
CASTILLO, M
LAM, YWF
DOOLEY, MA
STAHL, E
SMITH, PC
机构
[1] UNIV N CAROLINA,SCH PHARM,CHAPEL HILL,NC 27599
[2] UNIV N CAROLINA,DEPT MED,DIV RHEUMATOL,CHAPEL HILL,NC 27599
[3] UNIV TEXAS,COLL PHARM,AUSTIN,TX 78712
[4] UNIV TEXAS,HLTH SCI CTR,DIV CLIN PHARM,SAN ANTONIO,TX
关键词
D O I
10.1016/0009-9236(95)90226-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Ibuprofen is an over-the-counter nonsteroidal anti-inflammatory drug with a low incidence of severe adverse reactions, It is metabolized by oxidation to carboxyibuprofen and hydroxyibuprofen and by conjugation to an acyl glucuronide, In vitro studies have indicated that ibuprofen glucuronide is labile and reactive, forming covalent adducts with proteins, To verify the formation of ibuprofen-protein adducts in vivo, the pharmacokinetics of ibuprofen glucuronide and its covalent binding to plasma proteins were studied in five elderly patients who received long-term administration of oral doses of ibuprofen. Plasma levels of ibuprofen glucuronide were low relative to those of ibuprofen; the ratio of area under the plasma concentration versus time curve for the glucuronide relative to the parent drug was only 4%. Covalent binding of ibuprofen to plasma protein was observed in all patients, correlating well with the area under the plasma concentration versus time curve of ibuprofen glucuronide (r = 0.966), Compared with reports for other nonsteroidal anti-inflammatory drugs that form acyl glucuronides, plasma levels of ibuprofen-protein adduct are low during long-term administration, The observed lower reactivity in vivo is probably attributable to the greater stability of ibuprofen glucuronide relative to other acyl glucuronides.
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页码:636 / 644
页数:9
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