CYP3A4 and P-glycoprotein activity in healthy controls and transplant patients on cyclosporin vs. tacrolimus vs. sirolimus

被引:65
作者
Lemahieu, WPD
Maes, BD [1 ]
Verbeke, K
Vanrenterghem, Y
机构
[1] Katholieke Univ Leuven, Dept Med, Div Nephrol, Univ Hosp Gasthuisberg, Louvain, Belgium
[2] Katholieke Univ Leuven, Dept Med, Lab Radiopharmaceut Chem, Univ Hosp Gasthuisberg, Louvain, Belgium
关键词
calcineurin inhibitors; CYP3A4; P-glycoprotein; sirolimus;
D O I
10.1111/j.1600-6143.2004.00539.x
中图分类号
R61 [外科手术学];
学科分类号
摘要
This study aimed to determine the impact of maintenance immunosuppressive therapy with cyclosporin A (CsA), tacrolimus (FK506) and sirolimus (Rapa) on the in vivo activity of both intestinal and hepatic cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (PGP) in renal transplant patients. The activity of these four elimination pathways was measured by the recently validated intravenous (iv) and per oral (po)C-14 erythromycin breath and urine test. In addition, overall hepatic P450 activity was measured by the C-13 aminopyrin breath test. Three groups of stable renal transplant patients on maintenance therapy with corticosteroids (CS) and mycophenolate mofetil (MMF) plus either CsA or FK506 or Rapa were examined. A significant increase in intestinal CYP3A4 activity and a significant decrease in hepatic and intestinal PGP activity was seen in patients on CsA in comparison with those on FK506 or Rapa (p < 0.01). A similar analysis in six healthy volunteers at baseline and after intake of CsA, FK506 and Rapa confirmed the results seen in the patients. There was no difference in CYP3A4 and PGP activity in the patients taking either FK506 or Rapa and healthy controls. These data suggest that a different pattern of drug interactions might be expected in patients treated with CsA vs. FK506/Rapa.
引用
收藏
页码:1514 / 1522
页数:9
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