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In vivo higher glucuronidation of mycophenolic acid in male than in female recipients of a cadaveric kidney allograft and under immunosuppressive therapy with mycophenolate mofetil.
Ther Drug Monit. 2001 Oct; 23(5):520-5.TD

Abstract

Mycophenolate mofetil (MMF), an immunosuppressant drug used in organ transplantation to prevent rejection, is being used increasingly in association with cyclosporine and tacrolimus. Mycophenolic acid (MPA) is primarily metabolized in the liver to its 7-O-glucuronide (MPAG) derivative. The concentrations of MPAG in serum are many times the concentrations of MPA. Although MPAG has not shown immunosuppressant activity, it was postulated that it could displace MPA from its binding sites on albumin and hence increase the biologic effects of MPA. This effect could be important for patients with acute renal failure; under this condition, MPAG was shown to accumulate. The goal of this study was to document the MPAG/MPA concentration ratio in 100 renal transplant patients under a mixed immunosuppressive therapy. Further, the study addressed the question of whether MPAG can displace MPA in vivo from bound albumin in a representative renal transplant patient population under immunosuppressive therapy. Levels of MPAG and MPA were measured by high-performance liquid chromatography. The distribution of the ratios was not parametric as it tailed toward elevated values. After a square root transformation of the data, parametric analysis was possible. The average MPAG/MPA ratio was 15.0 +/- 2.2 for men versus 7.7 +/- 0.9 for women. Men treated with MMF and tacrolimus showed a lower ratio than patients treated with MMF and cyclosporine, confirming that tacrolimus inhibits glucuronidation of MPA. Further, it was determined that at physiologic concentrations, MPAG does not increase the amount of free MPA. Because MPAG can favor the elimination of MPA, it can be concluded that gender differences and cotreatment with tacrolimus must be taken into consideration when MMF is being administered.

Authors+Show Affiliations

Department of Biochemistry, Center Hospitalier de l'Université de Montréal, Notre-Dame Hospital, Montreal, Quebec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

11591897

Citation

Morissette, P, et al. "In Vivo Higher Glucuronidation of Mycophenolic Acid in Male Than in Female Recipients of a Cadaveric Kidney Allograft and Under Immunosuppressive Therapy With Mycophenolate Mofetil." Therapeutic Drug Monitoring, vol. 23, no. 5, 2001, pp. 520-5.
Morissette P, Albert C, Busque S, et al. In vivo higher glucuronidation of mycophenolic acid in male than in female recipients of a cadaveric kidney allograft and under immunosuppressive therapy with mycophenolate mofetil. Ther Drug Monit. 2001;23(5):520-5.
Morissette, P., Albert, C., Busque, S., St-Louis, G., & Vinet, B. (2001). In vivo higher glucuronidation of mycophenolic acid in male than in female recipients of a cadaveric kidney allograft and under immunosuppressive therapy with mycophenolate mofetil. Therapeutic Drug Monitoring, 23(5), 520-5.
Morissette P, et al. In Vivo Higher Glucuronidation of Mycophenolic Acid in Male Than in Female Recipients of a Cadaveric Kidney Allograft and Under Immunosuppressive Therapy With Mycophenolate Mofetil. Ther Drug Monit. 2001;23(5):520-5. PubMed PMID: 11591897.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo higher glucuronidation of mycophenolic acid in male than in female recipients of a cadaveric kidney allograft and under immunosuppressive therapy with mycophenolate mofetil. AU - Morissette,P, AU - Albert,C, AU - Busque,S, AU - St-Louis,G, AU - Vinet,B, PY - 2001/10/10/pubmed PY - 2002/1/5/medline PY - 2001/10/10/entrez SP - 520 EP - 5 JF - Therapeutic drug monitoring JO - Ther Drug Monit VL - 23 IS - 5 N2 - Mycophenolate mofetil (MMF), an immunosuppressant drug used in organ transplantation to prevent rejection, is being used increasingly in association with cyclosporine and tacrolimus. Mycophenolic acid (MPA) is primarily metabolized in the liver to its 7-O-glucuronide (MPAG) derivative. The concentrations of MPAG in serum are many times the concentrations of MPA. Although MPAG has not shown immunosuppressant activity, it was postulated that it could displace MPA from its binding sites on albumin and hence increase the biologic effects of MPA. This effect could be important for patients with acute renal failure; under this condition, MPAG was shown to accumulate. The goal of this study was to document the MPAG/MPA concentration ratio in 100 renal transplant patients under a mixed immunosuppressive therapy. Further, the study addressed the question of whether MPAG can displace MPA in vivo from bound albumin in a representative renal transplant patient population under immunosuppressive therapy. Levels of MPAG and MPA were measured by high-performance liquid chromatography. The distribution of the ratios was not parametric as it tailed toward elevated values. After a square root transformation of the data, parametric analysis was possible. The average MPAG/MPA ratio was 15.0 +/- 2.2 for men versus 7.7 +/- 0.9 for women. Men treated with MMF and tacrolimus showed a lower ratio than patients treated with MMF and cyclosporine, confirming that tacrolimus inhibits glucuronidation of MPA. Further, it was determined that at physiologic concentrations, MPAG does not increase the amount of free MPA. Because MPAG can favor the elimination of MPA, it can be concluded that gender differences and cotreatment with tacrolimus must be taken into consideration when MMF is being administered. SN - 0163-4356 UR - https://www.unboundmedicine.com/medline/citation/11591897/In_vivo_higher_glucuronidation_of_mycophenolic_acid_in_male_than_in_female_recipients_of_a_cadaveric_kidney_allograft_and_under_immunosuppressive_therapy_with_mycophenolate_mofetil_ L2 - http://dx.doi.org/10.1097/00007691-200110000-00004 DB - PRIME DP - Unbound Medicine ER -