title: 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.
authors.affiliation: West London Renal and Transplant Centre, London, UK. richard.borrows@uhb.nhs.uk
authors.forename: Richard
authors.initials: R
authors.lastname: Borrows
authors.forename: Gary
authors.initials: G
authors.lastname: Chusney
authors.forename: Marina
authors.initials: M
authors.lastname: Loucaidou
authors.forename: Anthony
authors.initials: A
authors.lastname: James
authors.forename: Jen
authors.initials: J
authors.lastname: Van Tromp
authors.forename: Tom
authors.initials: T
authors.lastname: Cairns
authors.forename: Megan
authors.initials: M
authors.lastname: Griffith
authors.forename: Nadey
authors.initials: N
authors.lastname: Hakim
authors.forename: Adam
authors.initials: A
authors.lastname: McLean
authors.forename: Andrew
authors.initials: A
authors.lastname: Palmer
authors.forename: Vassilios
authors.initials: V
authors.lastname: Papalois
authors.forename: David
authors.initials: D
authors.lastname: Taube
mesh_terms: D000284:Administration, Oral; D000658:Amoxicillin / Q000008:administration & dosage / Q000627:therapeutic use; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000627:therapeutic use; D019818:Clavulanic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D004359:Drug Therapy, Combination; D004764:Enterohepatic Circulation / Q000187:drug effects; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation; D016014:Linear Models; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D019818:Clavulanic Acid; D002939:Ciprofloxacin; D000658:Amoxicillin; D009173:Mycophenolic Acid