title: Mycophenolic acid-related diarrhea is not associated with polymorphisms in SLCO1B nor with ABCB1 in renal transplant recipients.
abstract: OBJECTIVE
  We investigated the association between genetic polymorphisms in ABCB1 and SLCO1B and mycophenolic acid (MPA) pharmacokinetics, and MPA-related diarrhea and leukopenia in 338 kidney transplant recipients.
  
  
  METHODS
  A total of 338 patients participating in an international, randomized-controlled clinical trial were genotyped for ABCB1 and SLCO1B. Patients were all treated with mycophenolate mofetil and either cyclosporine or tacrolimus. MPA-area under the curve (AUCs), MPA-glucuronide AUCs and acylglucuronide-AUCs were measured on days 3 and 10, and months 1, 3, 6, and 12 after kidney transplantation.
  
  
  RESULTS
  The risk of developing diarrhea was 1.8-fold higher in patients cotreated with tacrolimus compared with patients cotreated with cyclosporine (95% confidence interval: 1.03-3.13; P=0.038). ABCB1 and SLCO1B SNPs were not associated with dose-adjusted exposure to MPA, MPA-glucuronide, nor acylglucuronide-MPA nor with the incidence of diarrhea or leukopenia.
  
  
  CONCLUSIONS
  Genotyping for ABCB1 or SLCO1B pretransplantation is unlikely to be of clinical value for individualization of MPA therapy.
authors: PharmD, Department of Hospital Pharmacy, Erasmus Medical Center, P.O. Box 2040, CA Rotterdam 3000, The Netherlands. r.bouamar@erasmusmc.nl
authors: Rachida
authors: R
authors: Bouamar
authors: Dennis A
authors: DA
authors: Hesselink
authors: Ron H N
authors: RH
authors: van Schaik
authors: Willem
authors: W
authors: Weimar
authors: Ilse P
authors: IP
authors: van der Heiden
authors: Johannes W
authors: JW
authors: de Fijter
authors: Dirk R J
authors: DR
authors: Kuypers
authors: Teun
authors: T
authors: van Gelder
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002648:Child; D003967:Diarrhea / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D016030:Kidney Transplantation; D007970:Leukopenia / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects* / Q000493:pharmacokinetics; D009426:Netherlands / Q000453:epidemiology; D027361:Organic Anion Transporters / Q000235:genetics*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics*; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; C503999:SLCO1B1 protein, human; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D009173:Mycophenolic Acid