PMID- 20655577
OWN - NLM
STAT- MEDLINE
DCOM- 20110512
LR  - 20211020
IS  - 1532-866X (Electronic)
IS  - 0049-0172 (Print)
IS  - 0049-0172 (Linking)
VI  - 40
IP  - 4
DP  - 2011 Feb
TI  - Pharmacokinetics and pharmacodynamics of mycophenolic acid and their relation to 
      response to therapy of childhood-onset systemic lupus erythematosus.
PG  - 307-13
LID - 10.1016/j.semarthrit.2010.05.007 [doi]
AB  - OBJECTIVES: Mycophenolic acid (MPA) is the active form of mycophenolate mofetil 
      (MMF), which is currently used off-label as immunosuppressive therapy in 
      childhood-onset SLE (cSLE). The objectives of this study were to (1) characterize 
      the pharmacokinetics (MPA-PK) and pharmacodynamics (MPA-PD) of MPA and (2) 
      explore the relationship between MPA-PK and cSLE disease activity. METHODS: 
      MPA-PK [area under the curve from 0-12 hours (AUC(0-12))] and MPA-PD 
      [inosine-monophosphate dehydrogenase (IMPDH) activity] were evaluated in cSLE 
      patients on stable MMF dosing. Change in SLE disease activity while on MMF 
      therapy was measured using the British Isles Lupus Assessment Group (BILAG) 
      index. RESULTS: A total of 19 AUC(0-12) and 10 IMPDH activity profiles were 
      included in the analysis. Large interpatient variability in MPA exposure 
      (AUC(0-12)) was observed (mean +/- SE: 32 +/- 4.2 mg h/L; coefficient of variation: 
      57%). Maximum MPA serum concentrations coincided with maximum IMPDH inhibition. 
      AUC(0-12) and weight-adjusted MMF dosing were only moderately correlated (r = 
      0.56, P = 0.01). An AUC(0-12) of >/=30 mg h/L was associated with decreased BILAG 
      scores while on MMF therapy (P = 0.002). CONCLUSION: Weight-adjusted MMF dosing 
      alone does not reliably allow for the prediction of exposure to biologically 
      active MPA in cSLE. Individualized dosing considering MPA-PK appears warranted as 
      this allows for better estimation of immunologic suppression (IMPDH activity). 
      Additional controlled studies are necessary to confirm that an MPA AUC(0-12) of 
      at least 30 mg h/L is required for cSLE improvement.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Sagcal-Gironella, Anna Carmela P
AU  - Sagcal-Gironella AC
AD  - Division of Rheumatology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH 45229-3039, USA.
FAU - Fukuda, Tsuyoshi
AU  - Fukuda T
FAU - Wiers, Kristina
AU  - Wiers K
FAU - Cox, Shareen
AU  - Cox S
FAU - Nelson, Shannen
AU  - Nelson S
FAU - Dina, Blair
AU  - Dina B
FAU - Sherwin, Catherine M T
AU  - Sherwin CM
FAU - Klein-Gitelman, Marisa S
AU  - Klein-Gitelman MS
FAU - Vinks, Alexander A
AU  - Vinks AA
FAU - Brunner, Hermine I
AU  - Brunner HI
LA  - eng
GR  - 5K24HD050387/HD/NICHD NIH HHS/United States
GR  - UL1-RR026314/RR/NCRR NIH HHS/United States
GR  - U10 HD037249/HD/NICHD NIH HHS/United States
GR  - T32 AR007594/AR/NIAMS NIH HHS/United States
GR  - M01 RR008084-110237/RR/NCRR NIH HHS/United States
GR  - P60 AR047784-06A20005/AR/NIAMS NIH HHS/United States
GR  - P60 AR047784/AR/NIAMS NIH HHS/United States
GR  - UL1 RR026314/RR/NCRR NIH HHS/United States
GR  - M01 RR008084/RR/NCRR NIH HHS/United States
GR  - 5U10HD037249/HD/NICHD NIH HHS/United States
GR  - K24 HD050387/HD/NICHD NIH HHS/United States
GR  - P60-AR047884/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100723
PL  - United States
TA  - Semin Arthritis Rheum
JT  - Seminars in arthritis and rheumatism
JID - 1306053
RN  - 0 (Immunosuppressive Agents)
RN  - HU9DX48N0T (Mycophenolic Acid)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Area Under Curve
MH  - Child
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/pharmacokinetics/pharmacology/*therapeutic use
MH  - Lupus Erythematosus, Systemic/*drug therapy/metabolism
MH  - Male
MH  - Mycophenolic Acid/*analogs & 
      derivatives/*pharmacokinetics/pharmacology/therapeutic use
PMC - PMC3021770
MID - NIHMS235628
EDAT- 2010/07/27 06:00
MHDA- 2011/05/13 06:00
PMCR- 2012/02/01
CRDT- 2010/07/27 06:00
PHST- 2010/01/22 00:00 [received]
PHST- 2010/05/10 00:00 [revised]
PHST- 2010/05/10 00:00 [accepted]
PHST- 2010/07/27 06:00 [entrez]
PHST- 2010/07/27 06:00 [pubmed]
PHST- 2011/05/13 06:00 [medline]
PHST- 2012/02/01 00:00 [pmc-release]
AID - S0049-0172(10)00082-X [pii]
AID - 10.1016/j.semarthrit.2010.05.007 [doi]
PST - ppublish
SO  - Semin Arthritis Rheum. 2011 Feb;40(4):307-13. doi: 
      10.1016/j.semarthrit.2010.05.007. Epub 2010 Jul 23.