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Can xipamide or tacrolimus inhibit the glucuronidation of mycophenolic acid in rat liver slices?
Exp Toxicol Pathol. 2003 Jun; 54(5-6):375-9.ET

Abstract

The objective of this study was to investigate the effect of tacrolimus (Tac) and xipamide (X) on mycophenolic acid (MPA) glucuronidation in precision-cut rat liver slices. To assess a possible effect of these two drugs, the influence of the anti-inflammatory drug niflumic acid (NA)--a well-known inhibitor for MPA glucuronidation in human liver microsomes--was used as a standard. MPA and its main metabolite mycophenolic acid glucuronide (MPAG) were determined by means of high-performance liquid chromatography. MPA glucuronidation rate showed a significant linear correlation (p = 0.012) with MPA concentrations from 15.61 up to 124.88 microM in the medium. That means, the enzyme(s) responsible for the glucuronidation of MPA worked far below Km-value. With all MPA concentrations tested, neither the addition of Tac (31.30 nM) nor of X (28.25 nM) influenced the glucuronidation of MPA. In comparison, NA at a concentration of 70.92 nM showed a marked inhibitory effect (by 72%). The present pilot-study indicates that precision-cut rat liver slices are a suitable in vitro model to characterize the glucuronidation of MPA to its primary metabolite MPAG and interferences with other substances.

Authors+Show Affiliations

Institute of Clinical Pharmacology, Friedrich Schiller University Jena, Germany. annegret.balogh@med.uni-jena.deNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12877348

Citation

Balogh, Annegret, et al. "Can Xipamide or Tacrolimus Inhibit the Glucuronidation of Mycophenolic Acid in Rat Liver Slices?" Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Fur Toxikologische Pathologie, vol. 54, no. 5-6, 2003, pp. 375-9.
Balogh A, Merkel U, Müller D. Can xipamide or tacrolimus inhibit the glucuronidation of mycophenolic acid in rat liver slices? Exp Toxicol Pathol. 2003;54(5-6):375-9.
Balogh, A., Merkel, U., & Müller, D. (2003). Can xipamide or tacrolimus inhibit the glucuronidation of mycophenolic acid in rat liver slices? Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Fur Toxikologische Pathologie, 54(5-6), 375-9.
Balogh A, Merkel U, Müller D. Can Xipamide or Tacrolimus Inhibit the Glucuronidation of Mycophenolic Acid in Rat Liver Slices. Exp Toxicol Pathol. 2003;54(5-6):375-9. PubMed PMID: 12877348.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Can xipamide or tacrolimus inhibit the glucuronidation of mycophenolic acid in rat liver slices? AU - Balogh,Annegret, AU - Merkel,Ute, AU - Müller,Dieter, PY - 2003/7/25/pubmed PY - 2004/2/11/medline PY - 2003/7/25/entrez SP - 375 EP - 9 JF - Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie JO - Exp. Toxicol. Pathol. VL - 54 IS - 5-6 N2 - The objective of this study was to investigate the effect of tacrolimus (Tac) and xipamide (X) on mycophenolic acid (MPA) glucuronidation in precision-cut rat liver slices. To assess a possible effect of these two drugs, the influence of the anti-inflammatory drug niflumic acid (NA)--a well-known inhibitor for MPA glucuronidation in human liver microsomes--was used as a standard. MPA and its main metabolite mycophenolic acid glucuronide (MPAG) were determined by means of high-performance liquid chromatography. MPA glucuronidation rate showed a significant linear correlation (p = 0.012) with MPA concentrations from 15.61 up to 124.88 microM in the medium. That means, the enzyme(s) responsible for the glucuronidation of MPA worked far below Km-value. With all MPA concentrations tested, neither the addition of Tac (31.30 nM) nor of X (28.25 nM) influenced the glucuronidation of MPA. In comparison, NA at a concentration of 70.92 nM showed a marked inhibitory effect (by 72%). The present pilot-study indicates that precision-cut rat liver slices are a suitable in vitro model to characterize the glucuronidation of MPA to its primary metabolite MPAG and interferences with other substances. SN - 0940-2993 UR - https://www.unboundmedicine.com/medline/citation/12877348/Can_xipamide_or_tacrolimus_inhibit_the_glucuronidation_of_mycophenolic_acid_in_rat_liver_slices L2 - https://linkinghub.elsevier.com/retrieve/pii/S0940-2993(04)70119-0 DB - PRIME DP - Unbound Medicine ER -