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Inosine monophosphate dehydrogenase activity depends on plasma concentrations of mycophenolic acid and its glucuronides in kidney transplant recipients.
Clin Chim Acta. 2009 Nov; 409(1-2):56-61.CC

Abstract

BACKGROUND

Inosine 5'-monophosphate dehydrogenase (IMPDH) is a target of the immunosuppressant mycophenolic acid (MPA) which is used for the prevention of acute rejection. We evaluated the concentration-dependent effects of MPA and its phenolic (MPAG) and acyl (AcMPAG) glucuronides on IMPDH activity in erythrocytes in an initial and a stable phase.

METHODS

Eight kidney transplant recipients treated with mycophenolate mofetil (MMF) in an initial phase and 104 recipients [56 received MMF (MMF+) and 48 did not (MMF-)] in a stable phase were enrolled.

RESULTS

IMPDH activity in erythrocytes was inhibited at the peak plasma concentration of MPA in initial kidney transplant recipients. However, median IMPDH activity in erythrocytes was 1.73 times higher in MMF+ than in MMF- kidney transplant recipients (38.7 to 22.4 nmol/g hemoglobin/h, P<0.01). The median values of trough plasma concentrations (C(12)) of MPA, MPAG, and AcMPAG in stable kidney transplant recipients were 2.86, 49.9, and 0.256 microg/ml, respectively. In a multivariate analysis, AcMPAG C(12), MPAG C(12), MPA C(12), serum creatinine, age, lactate dehydrogenase, and serum albumin were significant predictors, accounting for interindividual variability of IMPDH (R(2)=0.537, P=0.02).

CONCLUSION

IMPDH activity in erythrocytes may be useful indicators of short-term immunosuppression and long-term exposure of MPA.

Authors+Show Affiliations

Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19723513

Citation

Mino, Yasuaki, et al. "Inosine Monophosphate Dehydrogenase Activity Depends On Plasma Concentrations of Mycophenolic Acid and Its Glucuronides in Kidney Transplant Recipients." Clinica Chimica Acta; International Journal of Clinical Chemistry, vol. 409, no. 1-2, 2009, pp. 56-61.
Mino Y, Naito T, Otsuka A, et al. Inosine monophosphate dehydrogenase activity depends on plasma concentrations of mycophenolic acid and its glucuronides in kidney transplant recipients. Clin Chim Acta. 2009;409(1-2):56-61.
Mino, Y., Naito, T., Otsuka, A., Ozono, S., Kagawa, Y., & Kawakami, J. (2009). Inosine monophosphate dehydrogenase activity depends on plasma concentrations of mycophenolic acid and its glucuronides in kidney transplant recipients. Clinica Chimica Acta; International Journal of Clinical Chemistry, 409(1-2), 56-61. https://doi.org/10.1016/j.cca.2009.08.016
Mino Y, et al. Inosine Monophosphate Dehydrogenase Activity Depends On Plasma Concentrations of Mycophenolic Acid and Its Glucuronides in Kidney Transplant Recipients. Clin Chim Acta. 2009;409(1-2):56-61. PubMed PMID: 19723513.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inosine monophosphate dehydrogenase activity depends on plasma concentrations of mycophenolic acid and its glucuronides in kidney transplant recipients. AU - Mino,Yasuaki, AU - Naito,Takafumi, AU - Otsuka,Atsushi, AU - Ozono,Seiichiro, AU - Kagawa,Yoshiyuki, AU - Kawakami,Junichi, Y1 - 2009/08/31/ PY - 2009/06/12/received PY - 2009/08/20/revised PY - 2009/08/20/accepted PY - 2009/9/3/entrez PY - 2009/9/3/pubmed PY - 2009/12/16/medline SP - 56 EP - 61 JF - Clinica chimica acta; international journal of clinical chemistry JO - Clin. Chim. Acta VL - 409 IS - 1-2 N2 - BACKGROUND: Inosine 5'-monophosphate dehydrogenase (IMPDH) is a target of the immunosuppressant mycophenolic acid (MPA) which is used for the prevention of acute rejection. We evaluated the concentration-dependent effects of MPA and its phenolic (MPAG) and acyl (AcMPAG) glucuronides on IMPDH activity in erythrocytes in an initial and a stable phase. METHODS: Eight kidney transplant recipients treated with mycophenolate mofetil (MMF) in an initial phase and 104 recipients [56 received MMF (MMF+) and 48 did not (MMF-)] in a stable phase were enrolled. RESULTS: IMPDH activity in erythrocytes was inhibited at the peak plasma concentration of MPA in initial kidney transplant recipients. However, median IMPDH activity in erythrocytes was 1.73 times higher in MMF+ than in MMF- kidney transplant recipients (38.7 to 22.4 nmol/g hemoglobin/h, P<0.01). The median values of trough plasma concentrations (C(12)) of MPA, MPAG, and AcMPAG in stable kidney transplant recipients were 2.86, 49.9, and 0.256 microg/ml, respectively. In a multivariate analysis, AcMPAG C(12), MPAG C(12), MPA C(12), serum creatinine, age, lactate dehydrogenase, and serum albumin were significant predictors, accounting for interindividual variability of IMPDH (R(2)=0.537, P=0.02). CONCLUSION: IMPDH activity in erythrocytes may be useful indicators of short-term immunosuppression and long-term exposure of MPA. SN - 1873-3492 UR - https://www.unboundmedicine.com/medline/citation/19723513/Inosine_monophosphate_dehydrogenase_activity_depends_on_plasma_concentrations_of_mycophenolic_acid_and_its_glucuronides_in_kidney_transplant_recipients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-8981(09)00446-X DB - PRIME DP - Unbound Medicine ER -