PMID- 19481022
OWN - NLM
STAT- MEDLINE
DCOM- 20090902
LR  - 20181201
IS  - 1557-3117 (Electronic)
IS  - 1053-2498 (Linking)
VI  - 28
IP  - 6
DP  - 2009 Jun
TI  - Proton pump inhibitor co-medication reduces mycophenolate acid drug exposure in 
      heart transplant recipients.
PG  - 605-11
LID - 10.1016/j.healun.2009.03.006 [doi]
AB  - BACKGROUND: Proton pump inhibitors (PPIs) are often prescribed for 
      gastrointestinal discomfort after heart transplantation (HTx). This study 
      investigates the impact of PPI use on mycophenolate acid (MPA) pharmacokinetics 
      in heart transplant recipients receiving mycophenolate mofetil (MMF) and 
      tacrolimus (Tac). METHODS: MPA post-dose plasma concentrations at 0 to 2 hours 
      were obtained by high-performance liquid chromatography (HPLC) in 21 patients on 
      pantoprazole 40 mg/day (PPI group) and 12 patients not on pantoprazole (control 
      group). In a subgroup, MPA plasma concentrations at 0 to 12 hours were measured 
      to evaluate full MPA area-under-the-curve (AUC) measurements. RESULTS: In the PPI 
      group, the mean daily MMF dose was 1,912 +/- 1,023 mg with mean pre-dose serum 
      concentrations (C(0)) of 1.9 +/- 1.4 mg/liter, without a significant difference 
      from controls. Mean post-dose MPA concentrations at 30 minutes (C(0.5h)) were 
      significantly higher in the control group (control, 17.9 +/- 11.5 mg/liter; PPI, 
      6.7 +/- 4.6 mg/liter; p < 0.001). One- and 2-hour (C(1h, 2h)) MPA concentrations 
      were persistently higher in the control group (1 hour: control, 13.8 +/- 9.1 
      mg/liter; PPI, 7.7 +/- 4.1 mg/liter; 2 hours: control, 7.6 +/- 4.2; PPI, 5.0 +/- 
      2.8 mg/liter; p < 0.05). In the subgroup with full AUC measurements, the control 
      group had higher MPA levels 12 hours after dosing (C(12h): control, 3.3 +/- 2.4 
      mg/liter; PPI, 1.6 +/- 1.3 mg/liter; p < 0.05) and a significantly higher 
      dose-adjusted AUC C(0-3h) (control, 59.5 +/- 20.7 mg/liter; PPI, 41.7 +/- 23.4 
      mg/liter; p < 0.05). In the subgroup, the maximum plasma concentration of 
      mycophenolic acid (MPA C(max)) in the PPI group was significantly lower (10.1 +/- 
      4.7 mg/liter) than in the control group (45.5 +/- 53.5 mg/liter, p < 0.0001), 
      whereas t(max) revealed no differences (control: 1.1 +/- 0.77 hours; PPI: 1.1 +/- 
      0.97 hours). Furthermore, a clear trend for more acute rejection episodes (AREs) 
      and more transplant vasculopathy (TVP) was found in the PPI group. CONCLUSIONS: 
      Patients with PPI co-medication show significantly lower MPA plasma 
      concentrations, possibly due to decreased absorption. Therapeutic drug monitoring 
      allows identification of patients with decreased MMF drug exposure who might be 
      at risk for acute rejection.
FAU - Kofler, Sieglinde
AU  - Kofler S
AD  - Department of Cardiac Surgery, University Hospital Grosshadern, Ludwig 
      Maximilians University, Marchioninistrasse 15, Munich, Germany. 
      sieglinde.kofler@med.uni-muenchen.de
FAU - Deutsch, Marcus-Andre
AU  - Deutsch MA
FAU - Bigdeli, Amir K
AU  - Bigdeli AK
FAU - Shvets, Nataliya
AU  - Shvets N
FAU - Vogeser, Michael
AU  - Vogeser M
FAU - Mueller, Thomas H
AU  - Mueller TH
FAU - Meiser, Bruno
AU  - Meiser B
FAU - Steinbeck, Gerhard
AU  - Steinbeck G
FAU - Reichart, Bruno
AU  - Reichart B
FAU - Kaczmarek, Ingo
AU  - Kaczmarek I
LA  - eng
PT  - Controlled Clinical Trial
PT  - Journal Article
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the 
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (2-Pyridinylmethylsulfinylbenzimidazoles)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Proton Pump Inhibitors)
RN  - D8TST4O562 (Pantoprazole)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - 2-Pyridinylmethylsulfinylbenzimidazoles/pharmacokinetics/*therapeutic use
MH  - Adult
MH  - Drug Interactions
MH  - Drug Therapy, Combination
MH  - Female
MH  - Gastrointestinal Diseases/drug therapy/etiology
MH  - Heart Transplantation/adverse effects/*immunology
MH  - Humans
MH  - Immunosuppressive Agents/pharmacokinetics/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Mycophenolic Acid/*analogs & derivatives/*blood/pharmacokinetics/therapeutic use
MH  - Pantoprazole
MH  - Proton Pump Inhibitors/pharmacokinetics/*therapeutic use
MH  - Tacrolimus/pharmacokinetics/*therapeutic use
MH  - Treatment Outcome
EDAT- 2009/06/02 09:00
MHDA- 2009/09/03 06:00
CRDT- 2009/06/02 09:00
PHST- 2008/10/06 00:00 [received]
PHST- 2009/01/23 00:00 [revised]
PHST- 2009/03/05 00:00 [accepted]
PHST- 2009/06/02 09:00 [entrez]
PHST- 2009/06/02 09:00 [pubmed]
PHST- 2009/09/03 06:00 [medline]
AID - S1053-2498(09)00153-3 [pii]
AID - 10.1016/j.healun.2009.03.006 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2009 Jun;28(6):605-11. doi: 
      10.1016/j.healun.2009.03.006.