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The magnitude and time course of changes in mycophenolic acid 12-hour predose levels during antibiotic therapy in mycophenolate mofetil-based renal transplantation.

Abstract：

:There is increasing evidence that monitoring predose plasma levels of mycophenolic acid (MPA) is of benefit in renal transplant recipients treated with mycophenolate mofetil (MMF). Concomitant treatment with oral antibiotics leads to a 10% to 30% reduction in MPA area under the curve (AUC)0-12, probably by reducing enterohepatic recirculation (EHR). Because of the timing of EHR (6 to 12 hours postdose), the magnitude of predose MPA level reduction may be disproportionately larger than that of AUC0-12. However, changes in predose MPA levels and the time course over which these changes occur and resolve during antibiotic treatment have not been studied. The purpose of this study was to define the extent and time course of MPA predose level reduction during antibiotic therapy. A total of 64 MMF-treated renal transplant recipients (with tacrolimus cotherapy) were prospectively studied. Clinically indicated cotherapy with either oral ciprofloxacin or amoxicillin with clavulanic acid resulted in a reduction in 12 hour predose MPA level to 46% of baseline within 3 days of antibiotic commencement. No demographic or biochemical variables were associated with the magnitude of MPA level reduction. No further fall in MPA level was seen by day 7, but MPA levels recovered spontaneously to 79% of baseline after 14 days of antibiotics. Levels normalized within 3 days of antibiotic cessation. No changes in daily MMF dose (normalized for body weight) were made during antibiotic treatment. This data should help the clinician to recognize the extent of MPA predose level reduction during antibiotic therapy, and to avoid inappropriate MMF dose escalation and potential risk of toxicity.

journal_name

Ther Drug Monit

journal_title

Therapeutic drug monitoring

authors

Borrows R,Chusney G,Loucaidou M,James A,Van Tromp J,Cairns T,Griffith M,Hakim N,McLean A,Palmer A,Papalois V,Taube D

doi

10.1097/FTD.0b013e31803111d5

subject

Has Abstract

pub_date

2007-02-01 00:00:00

pages

122-6

issue

eissn

0163-4356

issn

1536-3694

pii

00007691-200702000-00018

journal_volume

pub_type

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The magnitude and time course of changes in mycophenolic acid 12-hour predose levels during antibiotic therapy in mycophenolate mofetil-based renal transplantation.