Impact of changing from cyclosporine to tacrolimus on pharmacokinetics of mycophenolic acid in renal transplant recipients with diabetes.

Therapeutic Drug Monitoring
Jeong M ParkDiane M Cibrik

Abstract

The rate of mycophenolic acid (MPA) absorption after oral administration of mycophenolate mofetil (MMF) is delayed in patients with diabetes. Cyclosporine (CsA) decreases MPA exposure by inhibiting enterohepatic recirculation of MPA/MPA glucuronide, and tacrolimus (TRL) may alter the rate and extent of MPA absorption due to its prokinetic properties especially in patients with diabetic gastroparesis. This study evaluated the effect of changing from CsA to TRL on pharmacokinetics of MPA in stable renal transplant recipients with long-standing diabetes. Eight patients were switched from a stable dose of CsA to TRL while taking MMF 1 g twice daily. The 12-hour steady-state total plasma concentration-time profiles of MPA and MPA glucuronide were obtained after oral administration of MMF on 2 occasions: first while taking CsA and second after changing to TRL. Pharmacokinetic parameters of MPA were calculated by the noncompartmental method. Changing from CsA to TRL resulted in significantly increased MPA exposure (area under the concentration-time curve from 0 to 12 hours, AUC0-12) by 46 +/- 32% (P = 0.012) and MPA predose concentration (C0) by 121 +/- 67% (P = 0.008). The magnitude of change in MPA exposure did not correlate well wi...Continue Reading

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Citations

May 26, 2012·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·M CamilleriG Farrugia
Nov 14, 2012·The American Journal of Gastroenterology·Michael CamilleriUNKNOWN American College of Gastroenterology
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May 8, 2019·Journal of Clinical Pharmacology·Calvin J MeaneyKathleen M Tornatore
Jun 26, 2021·Journal of Clinical Pharmacology·Daniel BrazeauKathleen M Tornatore

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