Mycophenolate mofetil in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a prospective pharmacokinetics and clinical study.

Chaigne, B; Gatault, P; Darrouzain, F; Barbet, C; Degenne, D; François, M; Szymanski, P; Rabot, N; Golea, G; Diot, E; Maillot, F; Lebranchu, Y; Nivet, H; Paintaud, G; Halimi, J-M; Guillevin, L; Büchler, M

Chaigne, B; Gatault, P; Darrouzain, F; Barbet, C; Degenne, D; François, M; Szymanski, P; Rabot, N; Golea, G; Diot, E; Maillot, F; Lebranchu, Y; Nivet, H; Paintaud, G; Halimi, J-M; Guillevin, L; Büchler, M.

Afiliación

Chaigne B; Department of Immunology and Nephrology, Tours University Hospital, Tours, France; Department of Internal Medicine, Tours University Hospital, Tours, France; Université François Rabelais, Tours, France.

Clin Exp Immunol ; 176(2): 172-9, 2014 May.

Article en En | MEDLINE | ID: mdl-24304103

RESUMEN

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.

Asunto(s)

Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico; Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/metabolismo; Ácido Micofenólico/análogos & derivados; Ácido Micofenólico/farmacocinética; Adulto; Anciano; Anciano de 80 o más Años; Área Bajo la Curva; Inhibidores Enzimáticos/farmacocinética; Inhibidores Enzimáticos/uso terapéutico; Femenino; Humanos; Modelos Lineales; Recuento de Linfocitos; Masculino; Persona de Mediana Edad; Ácido Micofenólico/uso terapéutico; Estudios Prospectivos

Palabras clave

anti-neutrophil cytoplasmic antibody-associated vasculitis; mycophenolate mofetil; pharmacokinetics

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos / Ácido Micofenólico Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Exp Immunol Año: 2014 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido

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