title: Mycophenolate mofetil in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a prospective pharmacokinetics and clinical study.
abstract: Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) treatment strategy is based on immunosuppressive agents. Little information is available concerning mycophenolic acid (MPA) and the area under the curve (AUC) in patients treated for AAV. We evaluated the variations in pharmacokinetics for MPA in patients with AAV and the relationship between MPA-AUC and markers of the disease. MPA blood concentrations were measured through the enzyme-multiplied immunotechnique (C(0), C(30), C(1), C(2), C(3), C(4), C(6) and C(9)) to determine the AUC. Eighteen patients were included in the study. The median (range) MPA AUC(0-12) was 50·55 (30·9-105·4) mg/h/l. The highest coefficient of determination between MPA AUC and single concentrations was observed with C(3) (P < 0·0001) and C(2) (P < 0·0001) and with C(4) (P < 0·0005) or C(0) (P < 0·001). Using linear regression, the best estimation of MPA AUC was provided by a model including C(30), C(2) and C(4): AUC = 8·5 + 0·77 C(30) + 4·0 C(2) + 1·7 C(4) (P < 0·0001). Moreover, there was a significant relationship between MPA AUC(0-12) and lymphocyte count (P < 0·01), especially CD19 (P < 0·005), CD8 (P < 0·05) and CD56 (P < 0·05). Our results confirm the interindividual variability of MPA AUC in patients treated with MMF in AAV and support a personalized therapy according to blood levels of MPA.
authors.affiliation: Department of Immunology and Nephrology, Tours University Hospital, Tours, France; Department of Internal Medicine, Tours University Hospital, Tours, France; Université François Rabelais, Tours, France.
authors.forename: B
authors.initials: B
authors.lastname: Chaigne
authors.forename: P
authors.initials: P
authors.lastname: Gatault
authors.forename: F
authors.initials: F
authors.lastname: Darrouzain
authors.forename: C
authors.initials: C
authors.lastname: Barbet
authors.forename: D
authors.initials: D
authors.lastname: Degenne
authors.forename: M
authors.initials: M
authors.lastname: François
authors.forename: P
authors.initials: P
authors.lastname: Szymanski
authors.forename: N
authors.initials: N
authors.lastname: Rabot
authors.forename: G
authors.initials: G
authors.lastname: Golea
authors.forename: E
authors.initials: E
authors.lastname: Diot
authors.forename: F
authors.initials: F
authors.lastname: Maillot
authors.forename: Y
authors.initials: Y
authors.lastname: Lebranchu
authors.forename: H
authors.initials: H
authors.lastname: Nivet
authors.forename: G
authors.initials: G
authors.lastname: Paintaud
authors.forename: J-M
authors.initials: JM
authors.lastname: Halimi
authors.forename: L
authors.initials: L
authors.lastname: Guillevin
authors.forename: M
authors.initials: M
authors.lastname: Büchler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy* / Q000378:metabolism*; D019540:Area Under Curve; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016014:Linear Models; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011446:Prospective Studies
chemical_list: D004791:Enzyme Inhibitors; D009173:Mycophenolic Acid
keywords: anti-neutrophil cytoplasmic antibody-associated vasculitis; mycophenolate mofetil; pharmacokinetics