Please use this identifier to cite or link to this item: https://doi.org/10.1177/0091270009332813
Title: Mechanism-based enterohepatic circulation model of mycophenolic acid and its glucuronide metabolite: Assessment of impact of cyclosporine dose in asian renal transplant patients
Authors: Yau, W.-P. 
Vathsala, A.
Lou, H.-X.
Zhou, S.
Chan, E. 
Keywords: Cyclosporine
Enterohepatic circulation
Mycophenolic acid
Pharmacokinetic modeling
Renal transplant
Issue Date: Jun-2009
Citation: Yau, W.-P., Vathsala, A., Lou, H.-X., Zhou, S., Chan, E. (2009-06). Mechanism-based enterohepatic circulation model of mycophenolic acid and its glucuronide metabolite: Assessment of impact of cyclosporine dose in asian renal transplant patients. Journal of Clinical Pharmacology 49 (6) : 684-699. ScholarBank@NUS Repository. https://doi.org/10.1177/0091270009332813
Abstract: Mycophenolic acid (MPA) is mainly metabolized to MPA-glucuronide (MPAG), which may be reconverted to MPA following enterohepatic circulation (EHC). A physiologically realistic EHC model was proposed to estimate and assess the impact of cyclosporine (CsA) dose on the extent of EHC of MPA and MPAG. After the first oral dose of mycophenolate mofetil (MMF), theMPA and MPAG plasma concentration-time data of 14 adult renal transplant patients (12 receiving concomitant CsA and prednisolone and 2 receiving only concomitant prednisolone without CsA) were analyzed by individual pharmacokinetic modeling using a proposed 5-compartment drug and metabolite EHC model with a time-varying gallbladder emptying process. Simulations were performed to assess the influence of the time of bile release after dosing (T bile) and the gallbladder emptying interval (τ gall) on the EHC process. The extent of EHC for both MPA and MPAG tended to be lower in the group receiving CsA coadministration and decreased with increasing total body weight-adjusted CsA dose. Simulations revealed that T bjle and τ gall influenced the time of occurrence and maximum concentration of the second peak, as well as the extent of EHC, for MPA and MPAG. © 2009 the American College of Clinical Pharmacology.
Source Title: Journal of Clinical Pharmacology
URI: http://scholarbank.nus.edu.sg/handle/10635/106126
ISSN: 00912700
DOI: 10.1177/0091270009332813
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