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LAURENCE BONHOMME-FAIVRE, PHARM.D., PH.D., is Clinical Pharmacy Manager, Pharmacy–Pharmacology Service, Hôpital Paul Brousse (HPB), Villejuif, France, and Assistant Professor, School of Pharmacy, Université Paris Sud-11 (UPS), UPRES EA 2706, Chatenay Malabry, France. VERONIQUE PICARD, PHARM.D., PH.D., is Assistant Professor, School of Pharmacy, UPS. FAOUZI SALIBA, M.D., is Associate Professor of Pathology, Hepato-biliary Center; CHADI ABBARA, PHARM.D., is Staff Pharmacist, Pharmacy–Pharmacology Service; MADJID FODIL, PHARM.D., is Staff Pharmacist, Pharmacy–Pharmacology Service; and MELANIE CHAUNOY, PHARM.D., is Resident, Pharmacy–Pharmacology Service, HPB. ROBERT FARINOTTI, PHARM.D., PH.D., is Professor and Head, Department of Clinical Pharmacy, School of Pharmacy, UPS.

Address correspondence to Dr. Bonhomme-Faivre at the Service Pharmacie–Pharmacologie, Hôpital Paul Brousse, 12 Avenue Paul Vaillant Couturier, 94804 Villejuif Cedex, France (laurence.bonhomme-faivre{at}pbr.aphp.fr).

Purpose. The effect of ABCB1 3435C>T on tacrolimus concentrations in liver transplant recipients was studied. Tacrolimus is a substrate for P-glycoprotein, the product of the ABCB1 gene. To determine whether the ABCB1 single-nucleotide polymorphism (SNP) 3435C>T was associated with variation in the tacrolimus concentration:dose ratio (C:D) in 42 liver transplant recipients during three months after transplantation. Methods. Forty-two Caucasian patients who underwent an orthotopic liver transplantation from cadaveric donors received a basic immunosuppressive regimen containing tacrolimus and corticosteroids; mycophenolate mofetil was added in 18 cases. The SNP 3435C>T in exon 26 was investigated by MboI restriction-enzyme digestion, leading to the identification of CC, TT, or CT status at nucleotide 3435. Results obtained for the three genotypes were compared for each of three values: daily weight-adjusted tacrolimus dose, blood trough tacrolimus concentration, and C:D. Results. The wild-type genotype (3435CC) was observed in 10 patients (24%); 23 patients (55%) were heterozygous (3435CT) and 9 patients (21%) were homozygous for the mutation (3435TT). One to three days after liver transplantation, the mean ± S.D. C:D was significantly higher in subjects homozygous for the mutation compared with subjects with the wild-type allele (236 ± 119 ng · kg/mL · mg versus 104 ± 74 ng · kg/mL · mg, respectively; p = 0.0167). Subjects with the heterozygous allele had an intermediate mean ± S.D. C:D (131 ± 108 ng · kg/mL · mg). One or three months after transplantation, no significant difference in the tacrolimus C:D was evident among the three groups. Conclusion. The ABCB1 3435C>T polymorphism influenced the tacrolimus C:D in the first days after liver transplantation. Index terms: Blood levels; Dosage; Immunosuppressive agents; Mycophenolate mofetil; Pharmacokinetics; Polymorphisms; Steroids, cortico-; Tacrolimus; Transplantation