Mycophenolic acid area under the curve values in African American and Caucasian renal transplant patients are comparable

被引:114
作者
Shaw, LM
Korecka, M
Aradhye, S
Grossman, R
Bayer, L
Innes, C
Cucciara, A
Barker, C
Naji, A
Nicholls, A
Brayman, K
机构
[1] Univ Penn Hlth Syst, Dept Pathol & Lab Med, Philadelphia, PA USA
[2] Univ Penn Hlth Syst, Dept Surg, Philadelphia, PA USA
[3] Univ Penn Hlth Syst, Gen Clin Res Ctr, Philadelphia, PA USA
[4] Roche Global Res, Palo Alto, CA USA
关键词
D O I
10.1002/j.1552-4604.2000.tb05988.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The possibility of an effect of ethnicity on the pharmacokinetics of mycophenolic acid, the immunosuppressive metabolite of the prodrug mycophenolate mofetil, was studied over 90 days following renal transplantation in African American (n = 13) and Caucasian patients (n = 20). Since renal dysfunction and time after transplant surgery are two factors known to alter mycophenolic acid pharmacokinetics, two-way analysis of variance of the data at each time point with ethnicity and renal function status as covariates was used to evaluate the possibility of an ethnicity effect on the pharmacokinetic parameters. No statistically significant difference based on ethnicity was detected for the primary pharmacokinetic parameters, abbreviated mycophenolic acid area un der the concentration-time curve (MPA AUC), or the predose trough concentration on study days 4, 7, 14, 28, or 90. A statistically significant decrease in MPA AUC and increase in oral apparent clearance were observed in renally impaired patients regardless of ethnicity on days 4, and 4 and 7, respectively. The suggested mechanism for these differences is uremia-induced increased MPA free fraction, leading to a temporary increased clearance for this restrictively cleared drug.
引用
收藏
页码:624 / 633
页数:10
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