Pharmacokinetic profiling of cyclosporine microemulsion during the first 3 weeks after simultaneous pancreas-kidney transplantation.
The optimal effect of therapy with cyclosporine (CsA) seeks to minimize undesirable side effects while maximizing immunosuppression. This balance, depends on CsA exposure, which may be characterized by the area under the concentration-time-curve (AUC). Therefore, we tested the pharmacokinetic profile of microemulsion CsA as a superior approach to guide clinical immunosuppression after de novo simultaneous pancreas-kidney transplantations. We examined 10 consecutive pancreas-kidney recipients with type 1 diabetes and end-stage renal disease. All patients were treated with a regimen consisting of CsA, mycophenolate mofetil (MMF), and prednisone. Full (9-point) pharmacokinetic studies (C0, C1, C2, C3, C4, C6, C8, C10, C12) were performed on week 1 and during week 3 to examine CsA pharmacokinetic profiles. Mean AUC0-12 of 4431 +/- 2400 microg x h/L at week 1 remained stable at week 3 (5119 +/- 1190 microg x h/L). The C6 sampling time displayed the best correlation with AUC0-12 (r2 = 0.881), followed by C3 (r2 = 0.758). Our preliminary data after simultaneous pancreas-kidney transplantation support the hypothesis that C3 or C6 sampling is a more accurate predictor of the AUC0-12 than C0. The combination of two samplings, namely C3 + C6 (r2 = 0.938) or C2 + C6 (r2 = 0.955) proved excellent prediction of exposure after simultaneous pancreas-kidney transplantation.
Wacke
R
R
Institute of Clinical Pharmacology, University of Rostock, Rostock, Germany. rainer.wacke@med.uni-rostock.de
Kundt
G
G
Gock
M
M
Klar
E
E
Drewelow
B
B
Schareck
W
W
D019540:Area Under Curve; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D003928:Diabetic Nephropathies / Q000601:surgery; D004655:Emulsions; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D007408:Intestinal Absorption; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000276:immunology*; D009173:Mycophenolic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use; D016035:Pancreas Transplantation / Q000276:immunology*; D011184:Postoperative Period; D011241:Prednisone / Q000493:pharmacokinetics / Q000627:therapeutic use; D012044:Regression Analysis; D015203:Reproducibility of Results
D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D011241:Prednisone