肝硬化对布洛芬药代动力学性质的影响

THE EFFECTS OF HEPATIC CIRRHOSIS ON THE PHARMACOKINETICS OF IBUPROFEN IN MAN

6名健康人和6名酒精性肝硬化患者口服单剂量布洛芬消旋体片600mg。采用立体选择性高效液相色谱法测定两对映体血药浓度、尿中原形药物以及药物—葡萄糖醛酸结合物的排泄量。电子计算机拟合曲线,两组对映体达峰时间(t_(max))均在1.5h以内。肝病患者组两对映体的峰浓度(C_(max))均低于健康人组值,药物消除半衰期(t1/2)值比健康人值大一倍左右。尿中原形药物排泄量甚微。肝病患者两对映体葡萄糖醛酸结合型药物尿排泄量小于健康人值(p<0.001)。体内存在左旋体((-)—R—I)向右旋体((+)—S—I)的转换,但转换量较小,不足以引起体内(+)—S—I的血药浓度大幅度增加。肝硬化对布洛芬两对映体的体内过程有较大影响。

600mg of racemic ibuprofen was administered p. o. to six patients with alcoholichepatic cirrhosis and to six healthy subjects. A stereospecific HPLC assay was developed to measureplasma concentrations of both enantiomers of ibuprofen and amounts of both enantiomers excreted inunchanged and glucuronidated forms in urine. The absorption rate in both groups was alike as indicated by similar values of T_(max) Also C_(max) of(+)-(S)-enantiomer was significantly lower in patients with hepatic cirrhosis than in healthy subjects(p<0.001). The elimination of both enantiomers was singnificantly returded in the patients as indi-cated by its longer half-life than in controls ((-)-R-I:2.3 vs 1.4 hours: (+)-S-I: 3.3 vs 1.6hours). Only traces of unchanged enantiomers were recovered in the 12 hours urine sample. Theamounts of both enantiomers excreted in glucuronidated form were lower in patients than in controls.There was the unidirectional inversion from (-)-R-I to (+)-S-I, but amounts of inversion weresmall.