Pharmacokinetics and pharmacodynamics of intensified versus standard dosing of mycophenolate sodium in renal transplant patients

BACKGROUND AND OBJECTIVES: Adequate early mycophenolic acid (MPA) exposure is an important determinant for effective rejection prophylaxis. This pharmacokinetic study investigated whether an intensified dosing regimen of enteric-coated mycophenolate sodium (EC-MPS) could achieve higher mycophenolic...

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Main Authors: Glander, Petra (Author) , Sommerer, Claudia (Author) , Arns, Wolfgang (Author) , Ariatabar, Toofan (Author) , Kramer, Stefan (Author) , Vogel, Eva-Maria (Author) , Shipkova, Maria (Author) , Fischer, Wolfgang (Author) , Zeier, Martin (Author) , Budde, Klemens (Author)
Format: Article (Journal)
Language:English
Published: 2010 Feb 11
In: Clinical journal of the American Society of Nephrology
Year: 2010, Volume: 5, Issue: 3, Pages: 503-511
ISSN:1555-905X
Online Access: Get full text
Author Notes:Petra Glander, Claudia Sommerer, Wolfgang Arns, Toofan Ariatabar, Stefan Kramer, Eva-Maria Vogel, Maria Shipkova, Wolfgang Fischer, Martin Zeier, and Klemens Budde

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520 |a BACKGROUND AND OBJECTIVES: Adequate early mycophenolic acid (MPA) exposure is an important determinant for effective rejection prophylaxis. This pharmacokinetic study investigated whether an intensified dosing regimen of enteric-coated mycophenolate sodium (EC-MPS) could achieve higher mycophenolic acid (MPA) exposure early after transplantation versus a standard dosing regimen. - DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: De novo kidney transplant recipients (n = 75) who were treated with basiliximab induction and cyclosporine were randomly assigned to receive EC-MPS as either standard dosing (1440 mg/d; n = 37) or intensified dosing (days 0 through 14: 2880 mg/d; days 15 through 42: 2160 mg/d; followed by 1440 mg/d; n = 38). Full 12-hour pharmacokinetic and pharmacodynamic profiles were taken at six time points during the first 3 months. Exploratory analysis of inosine monophosphate dehydrogenase (IMPDH) activity was also performed for better understanding of the pharmacokinetic-pharmacodynamic relationship between MPA exposure and IMPDH activity in the early posttransplantation period. Preliminary efficacy parameters, safety, and tolerability were assessed. - RESULTS: Exposure to MPA was significantly higher on days 3 and 10 after transplantation in the intensified versus standard EC-MPS group, with 52.9 versus 22.2% (P < 0.05) of patients reaching MPA exposure >40 mg/h per L in the first week. The intensified regimen resulted in significantly lower IMPDH activity on day 3 after transplantation, and the overall safety was comparable for both groups. - CONCLUSIONS: These pharmacokinetic and safety data support further research on the hypothesis that early adequate MPA exposure could improve clinical outcome. 
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650 4 |a Area Under Curve 
650 4 |a Basiliximab 
650 4 |a Chi-Square Distribution 
650 4 |a Cyclosporine 
650 4 |a Drug Therapy, Combination 
650 4 |a Feasibility Studies 
650 4 |a Female 
650 4 |a Germany 
650 4 |a Graft Rejection 
650 4 |a Graft Survival 
650 4 |a Humans 
650 4 |a Immunosuppressive Agents 
650 4 |a IMP Dehydrogenase 
650 4 |a Kidney Transplantation 
650 4 |a Male 
650 4 |a Middle Aged 
650 4 |a Mycophenolic Acid 
650 4 |a Pilot Projects 
650 4 |a Prospective Studies 
650 4 |a Recombinant Fusion Proteins 
650 4 |a Tablets, Enteric-Coated 
650 4 |a Time Factors 
650 4 |a Treatment Outcome 
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