title: Diltiazem augments the influence of MDR1 genotype status on cyclosporine concentration in Chinese patients with renal transplantation.
abstract: OBJECTIVE
  Co-administration of diltiazem can reduce the dosage of cyclosporine (CsA) in patients with renal transplantation. In this study, we investigated how diltiazem altered the relationship between MDR1 genetic polymorphisms and CsA concentration in Chinese patients with renal transplantation.
  
  
  METHODS
  A total of 126 renal transplant patients were enrolled. All the patients received CsA (2-4 mg·kg(-1)·d(-1)), and diltiazem (90 mg/d) was co-administered to 76 patients. MDR1-C1236T, G2677T/A, and C3435T polymorphisms were genotyped. The whole blood concentration was measured using the FPIA method, and the adjusted trough concentrations were compared among the groups with different genotypes.
  
  
  RESULTS
  In all patients, MDR1-C1236T did not influence the adjusted CsA trough concentration. With regard to MDR1-3435, the adjusted CsA trough concentration was significantly higher in TT carriers than in CC and CT carriers when diltiazam was co-administered (58.83±13.95 versus 46.14±7.55 and 45.18±12.35 ng/mL per mg/kg, P=0.011), and the differences were not observed in patients without diltiazam co-administered. With regard to MDR1-2677, the adjusted CsA trough concentration was significantly higher in TT carriers than in GG and GT carriers when diltiazam was co-administered (61.31±12.93 versus 52.25±7.83 and 39.70±7.26 ng/mL per mg/kg, P=0.0001). The differences were also observed in patients without diltiazam co-administered (43.27±5.95 versus 35.22±7.55 and 29.54±5.35 ng/mL per mg/kg, P=0.001). The adjusted CsA trough blood concentration was significantly higher in haplotype T-T-T and haplotype T-T-C carriers than in non-carriers, regardless of diltiazem co-administered.
  
  
  CONCLUSIONS
  MDR1 variants influence the adjusted CsA trough concentration in Chinese patients with renal transplant, and the influence more prominent when diltiazem is co-administered.
authors.affiliation: 1] Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China [2] Department of Pharmacy, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.
authors.forename: Yi-xi
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Jia-li
authors.initials: JL
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Xue-ding
authors.initials: XD
authors.lastname: Wang
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Organ Transplant, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Chang-xi
authors.initials: CX
authors.lastname: Wang
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D065095:Calcineurin Inhibitors / Q000008:administration & dosage / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage* / Q000097:blood; D004110:Diltiazem / Q000008:administration & dosage* / Q000097:blood; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D065095:Calcineurin Inhibitors; D016572:Cyclosporine; D004110:Diltiazem