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: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2010 Feb 11
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| In: |
Clinical journal of the American Society of Nephrology
Year: 2010, Volume: 5, Issue: 3, Pages: 503-511 |
| ISSN: | 1555-905X |
| Online Access: |
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| Author Notes: | Petra Glander, Claudia Sommerer, Wolfgang Arns, Toofan Ariatabar, Stefan Kramer, Eva-Maria Vogel, Maria Shipkova, Wolfgang Fischer, Martin Zeier, and Klemens Budde |
| Summary: | 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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| Item Description: | Gesehen am 03.04.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1555-905X |