The relationship between the pharmacology of antiepileptic drugs and human gene variation: An overview

被引:45
作者
Ferraro, TN [1 ]
Buono, RJ
机构
[1] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA
[3] Univ Cincinnati, Dept Neurol, Cincinnati, OH 45267 USA
关键词
pharmacology; antiepileptic drugs; gene variation; anticonvulsant drugs; pharmacogenetics; pharmacogenomics; pharmacokinetics; pharamacodynamics; single nucleotide polymorphism;
D O I
10.1016/j.yebeh.2005.04.010
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Individual differences in clinical responsiveness to antiepileptic drugs are due to a complex interaction between environmental factors and genetic variation. Considerable interest has arisen in exploiting advances in molecular genetics to improve drug therapy for epilepsy and many other diseases; however, practical application of pharmacogenetics has been difficult to realize. Attempts to define gene variants that are associated with therapeutic (or adverse) effects of antiepileptic drugs rely currently on the prior identification of candidate genes and the subsequent evaluation of the distribution of allelic variants between individuals who have a "good" versus a "poor" clinical response. Many factors can adversely affect interpretation of such data, and careful consideration must be given to the design of genetic association studies involving candidate genes. Candidate genes may be identified in a number of ways; however, for studies of drugs, application of knowledge derived from basic pharmacology can suggest focused and testable hypotheses that are based on the fundamental principles of drug action. Thus, studies of genetic variation as they relate to proteins involved in antiepileptic drug kinetics and dynamics will identify key polymorphisms in endogenous molecules that determine degrees of drug efficacy and toxicity. Delineation of these effects in the coming years will promote enhanced success in the treatment of epilepsy. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:18 / 36
页数:19
相关论文
共 124 条
[11]   GENETICALLY-DETERMINED VARIABILITY IN ACETYLATION AND OXIDATION - THERAPEUTIC IMPLICATIONS [J].
CLARK, DWJ .
DRUGS, 1985, 29 (04) :342-375
[12]  
CLARK JA, 1994, MOL PHARMACOL, V46, P550
[13]   MULTIDRUG-RESISTANCE GENE (P-GLYCOPROTEIN) IS EXPRESSED BY ENDOTHELIAL-CELLS AT BLOOD-BRAIN BARRIER SITES [J].
CORDONCARDO, C ;
OBRIEN, JP ;
CASALS, D ;
RITTMANGRAUER, L ;
BIEDLER, JL ;
MELAMED, MR ;
BERTINO, JR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (02) :695-698
[14]   CHARACTERIZATION OF ETHOSUXIMIDE REDUCTION OF LOW-THRESHOLD CALCIUM CURRENT IN THALAMIC NEURONS [J].
COULTER, DA ;
HUGUENARD, JR ;
PRINCE, DA .
ANNALS OF NEUROLOGY, 1989, 25 (06) :582-593
[15]  
DEMORAIS SMF, 1994, J BIOL CHEM, V269, P15419
[16]  
DildyMayfield JE, 1996, J PHARMACOL EXP THER, V276, P1058
[17]   FORMATION OF ACTIVE METABOLITES OF ANTICONVULSANT DRUGS - A REVIEW OF THEIR PHARMACOKINETIC AND THEAPEUTIC SIGNIFICANCE [J].
EADIE, MJ .
CLINICAL PHARMACOKINETICS, 1991, 21 (01) :27-41
[18]   Effects of rifampicin and cimetidine on pharmacokinetics and pharmacodynamics of lamotrigine in healthy subjects [J].
Ebert, U ;
Thong, NQ ;
Oertel, R ;
Kirch, W .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 2000, 56 (04) :299-304
[19]   Gabapentin and vigabatrin increase GABA in the human neocortical slice [J].
Errante, LD ;
Williamson, A ;
Spencer, DD ;
Petroff, OAC .
EPILEPSY RESEARCH, 2002, 49 (03) :203-210
[20]  
Ferguson RJ, 1998, J PHARMACOL EXP THER, V284, P356