Pharmacokinetics and protein adduct formation of the pharmacologically active acyl glucuronide metabolite of mycophenolic acid in pediatric renal transplant recipients
| Autor: | Maria Shipkova, Eberhard Wieland, Paul Dieter Niedmann, Jane Haley, Victor W. Armstrong, Lutz T. Weber, Burkhard Tönshoff, Michael Oellerich |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Adolescent Stereochemistry Metabolite Blotting Western Glucuronidation Renal function Administration Oral Glucuronates Pharmacology Mycophenolate 030226 pharmacology & pharmacy Mycophenolic acid 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Glucuronides Pharmacokinetics medicine Humans Pharmacology (medical) Child Chromatography High Pressure Liquid Serum Albumin Chemistry Mycophenolic Acid Kidney Transplantation Transplantation 030220 oncology & carcinogenesis Area Under Curve Child Preschool Female Drug Monitoring Glucuronide Child Hospitalized Immunosuppressive Agents medicine.drug Protein Binding |
| Zdroj: | Therapeutic drug monitoring. 24(3) |
| ISSN: | 0163-4356 |
| Popis: | The acyl glucuronide metabolite (AcMPAG) of mycophenolic acid (MPA) has been found to possess both immunosuppressive and pro-inflammatory activity in vitro. In this study its pharmacokinetics were determined in pediatric renal transplant recipients receiving cyclosporine, steroids, and mycophenolate mofetil. Twelve-hour concentration-time profiles for AcMPAG, MPA, and the phenolic glucuronide (MPAG) were determined by high-performance liquid chromatography (HPLC) in the initial (1-3 wk; n = 16) and stable (3-12 mo; n = 22) phases after transplantation. In addition, the formation of covalent adducts between AcMPAG and plasma albumin (AcMPAG-Alb) was investigated using Western Blot analysis. AcMPAG-AUC(12h) showed significant (p < 0.05) correlations with MPA-AUC(12h) (r = 0.78) and MPAG-AUC(12h) (r = 0.78). In molar equivalents the median AcMPAG-AUC(12h) was 10.3% (range, 4.6%-45.5%) of MPA-AUC(12h). Values (median [range]) of AcMPAG-AUC(12h) (10.1 [3.30-30.1] mg.h/L), AcMPAG-C(0) (0.48 [0.08-1.43] mg/L), and AcMPAG-C(max) (1.95 [0.88-5.35] mg/L) were significantly (p < 0.05) higher in the stable phase than in the initial phase: 3.54 [2.07-20.0] mg.h/L for AUC(12h); 0.25 [ |
| Databáze: | OpenAIRE |
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