Population pharmacokinetics of mycophenolic acid and its main glucuronide metabolite: a comparison between healthy Chinese and Caucasian subjects receiving mycophenolate mofetil.
Purpose: Mycophenolate mofetil (MMF), a prodrug of the immunosuppressive agent mycophenolic acid (MPA), is widely used for prophylaxis of solid organ transplant rejection. MPA is primarily metabolized to 7- O-mycophenolic acid glucuronide (MPAG), an inactive metabolite that undergoes enterohepatic r...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 71; no. 1; pp. 95 - 107 |
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| Autores principales: | , , , |
| Formato: | equations & formulas research tables/charts Journal Article |
| Publicado: |
Springer Nature
Jan2015
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=103866196&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 103866196 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Jan2015 vid: 71 iid: 1 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 103866196 100209202 10.1007/s00228-014-1771-1 103866196 ppf: 95 ppct: 12 formats: fmt: @attributes: type: P tig: atl: Population pharmacokinetics of mycophenolic acid and its main glucuronide metabolite: a comparison between healthy Chinese and Caucasian subjects receiving mycophenolate mofetil. aug: au: Ling, Jing Shi, Jun Jiang, Qiudi Jiao, Zheng affil: Department of Pharmacy, Huashan Hospital, Fudan University, 12 Wu Lu Mu Qi M Road Shanghai China 200040 sug: subj: Mycophenolic Acid Pharmacokinetics Acids, Acyclic Pharmacokinetics Mycophenolate Mofetil Administration and Dosage Mycophenolate Mofetil Metabolism Mycophenolic Acid Metabolism Race Factors Human Chinese Persons White Persons Descriptive Statistics Data Analysis Software Chromatography, High Pressure Liquid Post Hoc Analysis Male Female Young Adult Adult Middle Age One-Way Analysis of Variance Correlation Coefficient Confidence Intervals Funding Source Adult: 19-44 years Middle Aged: 45-64 years Male Female ab: Purpose: Mycophenolate mofetil (MMF), a prodrug of the immunosuppressive agent mycophenolic acid (MPA), is widely used for prophylaxis of solid organ transplant rejection. MPA is primarily metabolized to 7- O-mycophenolic acid glucuronide (MPAG), an inactive metabolite that undergoes enterohepatic recirculation (EHC). This study assessed ethnic differences in the pharmacokinetics (PK) of MPA and MPAG between healthy Chinese and Caucasian subjects using population PK analysis. Methods: Data were pooled from 132 healthy subjects (80 Chinese, 52 Caucasians) in eight clinical studies in which MMF was administered in a single oral dose. Population PK analysis was performed using NONMEM®. Results: The PK of MPA and MPAG were best described by a five-chain compartment model, including a gallbladder compartment for EHC and a transit absorption model. Ethnicity was significantly correlated with the apparent clearance (CL/ F) and volume of distribution ( V/ F) of MPAG but not those of MPA. Weight was identified as a covariate and was correlated with the PK of MPA and MPAG. MPA CL/ F was 11.5 L/h for a 70-kg healthy subject, and the MPAG CL/ F values were 1.36 and 1.90 L/h for 70-kg Chinese and Caucasian individuals, respectively. Internal and external evaluation indicated model validity. Conclusions: This is the first population PK analysis to evaluate ethnic differences in the PK of MPA and MPAG in healthy Chinese and Caucasian subjects. No differences were observed in the PK of MPA between healthy Chinese and Caucasian subjects. Although, the MPAG CL/ F was approximately 40 % higher in Caucasians, this finding may not be clinically relevant. pubtype: Academic Journal doctype: equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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