Personalized immunosuppressive therapy in pediatric heart transplantation: Progress, pitfalls and promises

被引:15
作者
Xie, Hong-Guang [1 ]
机构
[1] Univ Calif San Francisco, Dept Biopharmaceut Sci, CDDS, Univ Calif Washington Ctr,Sch Pharm, Washington, DC 20036 USA
关键词
Immunosuppressants; Transplantation; Pharmacogenomics; Pharmacogenetics; Pharmacoethnics; Personalized medicine; MYCOPHENOLIC-ACID PHARMACOKINETICS; SINGLE-NUCLEOTIDE POLYMORPHISMS; THORACIC ORGAN RECIPIENTS; SAINT-JOHNS-WORT; AMIODARONE-CYCLOSPORINE INTERACTION; TACROLIMUS-BASED IMMUNOSUPPRESSION; UGT2B7 GENETIC POLYMORPHISMS; RENAL-ALLOGRAFT RECIPIENTS; GRAPEFRUIT JUICE; CARDIAC TRANSPLANTATION;
D O I
10.1016/j.pharmthera.2010.01.007
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The use of the immunosuppressants has revolutionized organ transplantation, including pediatric heart transplantation (PHTx). Recent evidence has shown that pharmacogenomics holds the promise to maximize the likelihood of drug safety and efficacy after the drug and dose are tailored individually based on the translation of pharmacogenomics to patient care. In this review, the immunosuppressants used for the PHTx are introduced, including their similarities and differences in immunosuppressive mechanisms of action, and their unique clinical efficacy and safety issues in relation to genetic polymorphisms in the genes that encode drug-metabolizing enzymes, drug transporters and drug targets. In addition, genetic susceptibility to severe drug-associated complications and strategies for their prevention and treatment are discussed. Moreover, clinically important drug-drug, drug-herb, or drug-food interactions and the effects of demographic and clinical covariates of recipients and donors on clinical endpoints of the PHTx are summarized, respectively. All relevant data are focused mainly on the PHTx. Information provided in this review would be useful for pediatric patient care, in particular for personalized medication, because each and every valuable piece could be fitted to the big picture of how organ rejection would be delayed and even avoided after personalized immunosuppressive therapy. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:146 / 158
页数:13
相关论文
共 170 条
[31]   IFN-γ gene polymorphisms associate with development of EBV+ lymphoproliferative disease in hu PBL-SCID mice [J].
Dierksheide, JE ;
Baiocchi, RA ;
Ferketich, AK ;
Roychowdhury, S ;
Pelletier, RP ;
Eisenbeis, CF ;
Caligiuri, MA ;
VanBuskirk, AM .
BLOOD, 2005, 105 (04) :1558-1565
[32]   Mycophenolate mofetil in pediatric heart transplant recipients: A single-center experience [J].
Dipchand, AI ;
Benson, L ;
McCrindle, BW ;
Coles, J ;
West, L .
PEDIATRIC TRANSPLANTATION, 2001, 5 (02) :112-118
[33]   Mycophenolic acid levels in pediatric heart transplant recipients receiving mycophenolate mofetil [J].
Dipchand, AI ;
Pietra, B ;
McCrindle, BW ;
Rosebrook-Bicknell, HL ;
Boucek, MM .
JOURNAL OF HEART AND LUNG TRANSPLANTATION, 2001, 20 (10) :1035-1043
[34]  
Dirks NL, 2004, INT J CLIN PHARM TH, V42, P701
[35]   Sirolimus population pharmacokinetic/pharmacogenetic analysis and Bayesian modelling in kidney transplant recipients [J].
Djebli, Nassim ;
Rousseau, Annick ;
Hoizey, Guillaume ;
Rerolle, Jean-Philippe ;
Toupance, Olivier ;
Le Meur, Yann ;
Marquet, Pierre .
CLINICAL PHARMACOKINETICS, 2006, 45 (11) :1135-1148
[36]   Coordinate induction of both cytochrome P4503A and MDRI by St John's wort in healthy subjects [J].
Dresser, GK ;
Schwarz, UI ;
Wilkinson, GR ;
Kim, RB .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2003, 73 (01) :41-50
[37]   The effects of fruit juices on drug disposition: a new model for drug interactions [J].
Dresser, GK ;
Bailey, DG .
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 2003, 33 :10-16
[38]   TROUGH CONCENTRATIONS OF CYCLOSPORINE IN BLOOD FOLLOWING ADMINISTRATION WITH GRAPEFRUIT JUICE [J].
DUCHARME, MP ;
PROVENZANO, R ;
DEHOORNESMITH, M ;
EDWARDS, DJ .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1993, 36 (05) :457-459
[39]   DISPOSITION OF INTRAVENOUS AND ORAL CYCLOSPORINE AFTER ADMINISTRATION WITH GRAPEFRUIT JUICE [J].
DUCHARME, MP ;
WARBASSE, LH ;
EDWARDS, DJ .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1995, 57 (05) :485-491
[40]   St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4 [J].
Dürr, D ;
Stieger, B ;
Kullak-Ublick, GA ;
Rentsch, KM ;
Steinert, HC ;
Meier, PJ ;
Fattinger, K .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2000, 68 (06) :598-604