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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).
CONCLUSION
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].

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    • Authors

    Cai J, Huang Z, Yang G, Cheng K, Ye Q, Ming Y, Zuo X, Zhou P, Yuan H

    Institution

    Center of Clinical Pharmacology of the Third Xiangya Hospital, Central South University, Changsha, China.

    Source

    American journal of cardiovascular drugs : drugs, devices, and other interventions 11:6 2011 Dec 1 pg 401-9

    MeSH

    Adult
    Amlodipine
    Antihypertensive Agents
    Blood Pressure
    Cyclosporine
    Cytochrome P-450 CYP3A
    Double-Blind Method
    Drug Interactions
    Female
    Genotype
    Humans
    Hypertension
    Immunosuppressive Agents
    Kidney Transplantation
    Male
    P-Glycoprotein
    Polymerase Chain Reaction
    Polymorphism, Restriction Fragment Length
    Prospective Studies
    Tetrazoles
    Valine

    Pub Type(s)

    Comparative Study
    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22149319