PMID- 19519820
OWN - NLM
STAT- MEDLINE
DCOM- 20091104
LR  - 20230124
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Linking)
VI  - 9
IP  - 7
DP  - 2009 Jul
TI  - Proton pump inhibitors reduce mycophenolate exposure in heart transplant 
      recipients-a prospective case-controlled study.
PG  - 1650-6
LID - 10.1111/j.1600-6143.2009.02682.x [doi]
AB  - This prospective study investigates the impact of proton pump inhibitors (PPI) on 
      mycophenolic acid (MPA) pharmacokinetics in heart transplant recipients receiving 
      mycophenolate mofetil (MMF) and tacrolimus. MPA plasma concentrations at baseline 
      (C(0 h)), 30 min (C(0.5 h)), 1(C(1 h)) and 2 h (C(2 h)) were obtained by 
      high-performance liquid chromatography (HPLC) in 22 patients treated with 
      pantoprazole 40 mg and MMF 2000 mg. Measurements were repeated 1 month after 
      pantoprazole withdrawal. A four-point limited-sampling strategy was applied to 
      calculate the MPA area under the curve (MPA-AUC). Predose MPA concentrations with 
      PPI were 2.6 +/- 1.6 mg/L versus 3.4 +/- 2.7 mg/L without PPI (p = ns). Postdose 
      MPA concentrations were lower with PPI at C(0.5 h) (8.3 +/- 5.7 mg/L vs. 18.3 +/- 
      11.3 mg/L, p = 0.001) and C(1 h) (10.0 +/- 5.6 mg/L vs. 15.8 +/- 8.4 mg/L, p = 
      0.004), without significant differences at C(2 h) (8.3 +/- 6.5 mg/L vs. 7.6 +/- 
      3.9 mg/L). The MPA-AUC was significantly lower with PPI medication (51.2 +/- 26.6 
      mg x h/L vs. 68.7 +/- 30.3 mg x h/L; p = 0.003). The maximum concentration of MPA 
      (MPA-C(max)) was lower (12.2 +/- 7.5 mg/L vs. 20.6 +/- 9.3 mg/L; p = 0.001) and 
      the time to reach MPA-C(max) (t(max)) was longer with PPI (60.0 +/- 27.8 min vs. 
      46.4 +/- 22.2 min; p = 0.05). This is the first study to document an important 
      drug interaction between a widely used immunosuppressive agent and a class of 
      drugs frequently used in transplant patients. This interaction results in a 
      decreased MMF drug exposure which may lead to patients having a higher risk for 
      acute rejection and transplant vasculopathy.
FAU - Kofler, S
AU  - Kofler S
AD  - Department of Cardiac Surgery, University Hospital Grosshadern, Ludwig 
      Maximilians University Munich, Munich, Germany.
FAU - Shvets, N
AU  - Shvets N
FAU - Bigdeli, A K
AU  - Bigdeli AK
FAU - Konig, M A
AU  - Konig MA
FAU - Kaczmarek, P
AU  - Kaczmarek P
FAU - Deutsch, M-A
AU  - Deutsch MA
FAU - Vogeser, M
AU  - Vogeser M
FAU - Steinbeck, G
AU  - Steinbeck G
FAU - Reichart, B
AU  - Reichart B
FAU - Kaczmarek, I
AU  - Kaczmarek I
LA  - eng
PT  - Journal Article
DEP - 20090610
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
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/administration & dosage/adverse effects
MH  - Acute Disease
MH  - Adult
MH  - Case-Control Studies
MH  - Drug Interactions
MH  - Drug Therapy, Combination
MH  - Female
MH  - Graft Rejection/etiology
MH  - *Heart Transplantation/physiology
MH  - Humans
MH  - Immunosuppressive Agents/*administration & dosage/pharmacokinetics
MH  - Male
MH  - Middle Aged
MH  - Mycophenolic Acid/administration & dosage/*analogs & 
      derivatives/pharmacokinetics/pharmacology
MH  - Pantoprazole
MH  - Prospective Studies
MH  - Proton Pump Inhibitors/*administration & dosage/*adverse effects
MH  - Risk Factors
MH  - Tacrolimus/administration & dosage
EDAT- 2009/06/13 09:00
MHDA- 2009/11/05 06:00
CRDT- 2009/06/13 09:00
PHST- 2009/06/13 09:00 [entrez]
PHST- 2009/06/13 09:00 [pubmed]
PHST- 2009/11/05 06:00 [medline]
AID - S1600-6135(22)01747-6 [pii]
AID - 10.1111/j.1600-6143.2009.02682.x [doi]
PST - ppublish
SO  - Am J Transplant. 2009 Jul;9(7):1650-6. doi: 10.1111/j.1600-6143.2009.02682.x. 
      Epub 2009 Jun 10.