title: Relationship between the Peripheral Lymphocyte Response to Mycophenolic Acid in vitro and the Level of ATP in Peripheral CD4+ Lymphocytes before and after Renal Transplantation.
abstract: OBJECTIVE
  The lymphocyte immunosuppressant sensitivity test has been used to predict the pharmacodynamics of immunosuppressive drugs for the purpose of preventing acute rejection and infection after renal transplantation. On the other hand, measuring the ATP levels in peripheral CD4+ lymphocytes is also able to monitor the risks of rejection and infection in transplant recipients. In the present study, we examined the relationship between the mycophenolic acid pharmacodynamics and the ATP levels in peripheral lymphocytes before and after renal transplantation.
  
  
  METHODS
  We examined both the pharmacological efficacy of mycophenolic acid and the lymphocyte ATP levels before and 2, 4 and 6 weeks after the operation in 20 renal transplant recipients. The drug's pharmacological efficacy was evaluated by the 50% inhibitory concentration of the drug against the in vitro proliferation of peripheral blood lymphocytes activated by T cell mitogen. The ATP levels in peripheral CD4+ lymphocytes were measured by the Immuknow assay kit. The relationships between the mycophenolic acid pharmacodynamics and ATP levels in peripheral lymphocytes were examined in these recipients.
  
  
  RESULTS
  The immunosuppressive effects of mycophenolic acid against mitogen-activated lymphocyte proliferation were significantly and positively correlated with the lymphocyte ATP levels, but only at 6 weeks after transplantation. The relationship was not significant before or at 2 or 4 weeks after the operation.
  
  
  CONCLUSIONS
  Our present data raised the possibility that evaluating the pharmacological efficacy of mycophenolic acid pre-transplantation and monitoring the ATP level 6 weeks after transplantation can predict the risk of rejection and/or infection in renal transplant recipients.
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: Division of Pharmacy, Niigata University Medical and Dental Hospital, Niigata, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tsukaguchi
authors.affiliation: Division of Pharmacy, Niigata University Medical and Dental Hospital, Niigata, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sasahara
authors.affiliation: Division of Pharmacy, Niigata University Medical and Dental Hospital, Niigata, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Isogai
authors.affiliation: Division of Pharmacy, Niigata University Medical and Dental Hospital, Niigata, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Toyama
authors.affiliation: Division of Pharmacy, Niigata University Medical and Dental Hospital, Niigata, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Satoh
authors.affiliation: Division of Urology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Saito
authors.affiliation: Division of Urology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Division of Urology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Onda
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000379:methods*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008934:Mitogens / Q000037:antagonists & inhibitors; D009173:Mycophenolic Acid / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D008934:Mitogens; D000255:Adenosine Triphosphate; D009173:Mycophenolic Acid