Gwilt P R, Radick L E, Li X Y, Whalen J J, Leaf C D
Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha 68198-6025, USA.
J Clin Pharmacol. 1998 Oct;38(10):945-50. doi: 10.1002/j.1552-4604.1998.tb04391.x.
The pharmacokinetics of both 2-oxothiazolidine-4-carboxylate (OTZ), a prodrug of cysteine, and total blood cysteine (cysteine plus cystine) were investigated in 18 healthy volunteers. OTZ was given either as a single, 2-hour intravenous infusion (56-66 mg/kg) or similarly infused (70-100 mg/kg) every 8 hours for four doses. Blood was assayed for OTZ, total blood cysteine, and glutathione. The pharmacokinetics of OTZ were analyzed alone and simultaneously with total cysteine using the NONMEM software package (University of California at San Francisco. The pharmacokinetics of OTZ were best described by Michaelis-Menten kinetics with parallel first-order elimination. OTZ was efficiently removed from the plasma. The Michaelis-Menten route of elimination was attributed to conversion of OTZ to total cysteine. At plasma OTZ concentrations equal to the Michaelis constant Km, 84% of OTZ was converted to total cysteine. These findings suggest that OTZ administered intravenously is an efficient means of increasing total blood cysteine.
在18名健康志愿者中研究了半胱氨酸前体药物2-氧代噻唑烷-4-羧酸盐（OTZ）和全血半胱氨酸（半胱氨酸加胱氨酸）的药代动力学。OTZ以单次2小时静脉输注（56 - 66 mg/kg）给药，或以同样方式每8小时输注一次（70 - 100 mg/kg），共给药四次。检测血液中的OTZ、全血半胱氨酸和谷胱甘肽。使用NONMEM软件包（加利福尼亚大学旧金山分校）单独分析OTZ的药代动力学，并与总半胱氨酸同时分析。OTZ的药代动力学最好用具有平行一级消除的米氏动力学来描述。OTZ能有效地从血浆中清除。米氏消除途径归因于OTZ转化为总半胱氨酸。在血浆OTZ浓度等于米氏常数Km时，84%的OTZ转化为总半胱氨酸。这些发现表明静脉注射OTZ是增加全血半胱氨酸的有效方法。
