摘要
目的探讨性别对肾移植患者霉酚酸酯（MMF）药代动力学的影响。方法纳入肾移植科手术患者178例。当体内药物浓度到达稳态后,于服药后0.5,1.5,4和9 h取患者静脉血,用高效液相色谱法测定血浆中MMF代谢物霉酚酸（MPA）和葡萄糖醛酸霉酚酸（MPAG）浓度,估算0-12 h血药浓度-时间曲线下面积（AUC0-12 h）。结果女性剂量调整MPA AUC0-12 h（46.24±2.98）mg·h·L-1·g-1,显著高于男性的（35.36±1.61）mg·h·L-1·g-1（P〈0.01）;而MPAG/MPA女性（15.24±1.05）显著低于男性（18.68±0.87）（P〈0.05）。此外,女性年龄与剂量调整MPA AUC0-12 h呈负相关（P〈0.05）,45岁以下年龄组的剂量调整MPA AUC0-12h（49.74±3.58）mg·h·L-1·g-1,显著高于45岁以上年龄组的（33.69±2.49）mg·h·L-1·g-1（P〈0.05）。结论在中国肾移植患者中,MMF体内代谢存在性别差异,且女性体内药物代谢与年龄相关。
Objective To investigate the gender- related differences of mycophenolate mofetil pharmacokinetics in Chinese renal transplant patients. Methods A total of 178 renal transplant patients were included in the study. Blood samples were taken at 0. 5,1. 5,4 and 9 hours after the morning dose. A validated HPLC method was used to simultaneously detect MPA and MPAG concentrations in plasma,and AUC0- 12 hof MPA and MPAG were calculated. Results The dose- adjusted AUC0- 12 hof MPA was significantly higher in female patients（ 46. 24 ± 2. 98）mg·h·L- 1·g- 1than that in male patients（ 35. 36 ± 1. 61） mg·h·L- 1·g- 1（ P〈 0. 05）,while MPAG/MPA ratio was the opposite（ 15. 24 ± 1. 05 vs.18. 68 ± 0. 87,P〈 0. 05）. What＇s more,there was a negative correlation between age and dose- adjusted AUC0- 12 hof MPA（ P〈 0. 05） in female patients. Younger female（ age 45） patients had higher dose- adjusted AUC0- 12 hof MPA（ 49. 74 ± 3. 58） mg · h · L- 1·g- 1than older female（ age 45） patients（ 33. 69 ± 2. 49） mg·h·L- 1·g- 1（ P〈 0. 05）.Conclusion Gender- related differences in MMF pharmacokinetics were found in our study,and dose- adjusted AUC0- 12 hof MPA was negatively correlated with age in female patients.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2015年第6期456-458,462,共4页
The Chinese Journal of Clinical Pharmacology
基金
"十二五"国家科技重大专项基金资助项目(2012ZX09506001-004)
国家自然科学基金资助项目(81102515
81320108027
81173131)
广东省重点实验室建设基金资助项目(2011A060901014)
广东省重大科技专项基金资助项目(2011A080300001
2012A080202013)
关键词
霉酚酸酯
葡萄糖醛酸转移酶
肾移植
药代动力学
性别
mycophenolate mofetil
glucuronosyltransferases
renal transplantation
pharmacokinetic
gender
