title: Comparing antihypertensive effect and plasma ciclosporin concentration between amlodipine and valsartan regimens in hypertensive renal transplant patients receiving ciclosporin therapy.
abstract: BACKGROUND
  Hypertension, a major complication in kidney transplant recipients, is associated with premature death and graft loss. However, an optimal antihypertensive therapy for these patients has not been established [Chinese Clinical Trial Registry No. ChiCTR-TRC-10001071].
  
  
  OBJECTIVE
  The aim of the present study was to evaluate the effect of amlodipine and valsartan on BP control in renal transplant patients and to analyze the correlation between cytochrome P450 (CYP) 3A5 or multidrug resistance-1 gene (MDR1) genotype and the antihypertensive effect of these two regimens.
  
  
  METHODS
  150 renal transplant patients with stage 1 or 2 hypertension were enrolled in the trial. Patients were randomly assigned to amlodipine or valsartan. Metoprolol was added if BP was not under control after 4 weeks. BP and plasma levels of ciclosporin were monitored during the 24-week trial. CYP3A5 and MDR1 genotypes were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
  
  
  RESULTS
  The demographic features and baseline BP were similar between these two groups. During the 24-week trial, the reduction of systolic BP (SBP) was similar between the amlodipine and valsartan groups. However, the reduction of diastolic BP (DBP) was significantly greater in the amlodipine group compared with the valsartan group at 12, 16, and 24 weeks of treatment. The plasma level of ciclosporin at 2 hours of medication was significantly higher in the amlodipine group than in the valsartan group after 4 weeks of the trial. The reduction of DBP at 24 weeks was greater in the subjects with CYP3A5 *3/*3 variant than in those with CYP3A5*1/*1 variant (-13.5 ± 1.9 mmHg vs -8.7 ± 1.6 mmHg, p < 0.05).
  
  
  CONCLUSIONS
  The present study demonstrated that amlodipine produced a greater reduction of DBP than valsartan, although both amlodipine and valsartan resulted in satisfactory control of BP in patients with renal transplantation. Administration of amlodipine significantly increased the plasma concentration of ciclosporin, and its effects on BP control and ciclosporin concentration may be associated with the CYP3A5 genotype in these subjects [Chinese Clinical Trial Registry No. ChiCTR-TRC-10001071].
authors.affiliation: Center of Clinical Pharmacology of the Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cai
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Huang
authors.forename: Guoping
authors.initials: G
authors.lastname: Yang
authors.forename: Ke
authors.initials: K
authors.lastname: Cheng
authors.forename: Qifa
authors.initials: Q
authors.lastname: Ye
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Ming
authors.forename: Xiaocong
authors.initials: X
authors.lastname: Zuo
authors.forename: Peipei
authors.initials: P
authors.lastname: Zhou
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D016572:Cyclosporine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000959:Antihypertensive Agents; D007166:Immunosuppressive Agents; D013777:Tetrazoles; D017311:Amlodipine; D000068756:Valsartan; D016572:Cyclosporine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D014633:Valine