Influence of the CYP3A5 genotype on tacrolimus pharmacokinetics and pharmacodynamics in young kidney transplant recipients. 2007

Mariano Ferraresso, and Amedea Tirelli, and Luciana Ghio, and Paolo Grillo, and Valentina Martina, and Erminio Torresani, and Alberto Edefonti
Department of Surgical Sciences, University of Milan, Medical School, Milan, Italy. mariano.ferraresso@unimi.it

CYP3A enzyme plays a pivotal role in TAC metabolism. The aim of this study was to analyze retrospectively the influence of CYP3A5 gene polymorphism on TAC pharmacokinetics and pharmacodynamics in 30 teenage kidney transplant recipients. TAC dose, trough blood levels, apparent volume of distribution, as well as blood pressure and antihypertensive therapy obtained at different post-transplant periods, were correlated with the corresponding genotype. Despite a therapeutic monitoring strategy, heterozygotes (CYP3A5*1/*3) displayed a lower TAC blood concentration compared with homozygotes (CYP3A5*3/*3). Therefore, a two-fold increase of the daily TAC dose was required in the heterozygotes to reach the desired therapeutic target level. A significant group by time interaction effect was present for both variables (repeated measures ANOVA: p = 0.002) meaning a significant different pharmacokinetic response in these two cohorts. Mean blood pressure was also elevated in CYP3A5*1/*3 recipients despite similar antihypertensive treatment. This was parallel with an elevated apparent volume of distribution of TAC in this group. Thus, the allele-effect was correlated with one of the most common TAC side-effects suggesting a possible influence of CYP3A5 polymorphism on TAC pharmacodynamics. The authors concluded that a pre-emptive CYP3A5 pharmacogenetic screening could contribute to better individualization of TAC therapy.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000293 Adolescent A person 13 to 18 years of age. Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D012189 Retrospective Studies Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. Retrospective Study,Studies, Retrospective,Study, Retrospective

Related Publications

Mariano Ferraresso, and Amedea Tirelli, and Luciana Ghio, and Paolo Grillo, and Valentina Martina, and Erminio Torresani, and Alberto Edefonti
January 2015, SpringerPlus,
Mariano Ferraresso, and Amedea Tirelli, and Luciana Ghio, and Paolo Grillo, and Valentina Martina, and Erminio Torresani, and Alberto Edefonti
February 2007, Clinical pharmacology and therapeutics,
Mariano Ferraresso, and Amedea Tirelli, and Luciana Ghio, and Paolo Grillo, and Valentina Martina, and Erminio Torresani, and Alberto Edefonti
August 2017, Journal of clinical pharmacy and therapeutics,
Mariano Ferraresso, and Amedea Tirelli, and Luciana Ghio, and Paolo Grillo, and Valentina Martina, and Erminio Torresani, and Alberto Edefonti
August 2019, Pediatric transplantation,
Mariano Ferraresso, and Amedea Tirelli, and Luciana Ghio, and Paolo Grillo, and Valentina Martina, and Erminio Torresani, and Alberto Edefonti
December 2019, Progress in transplantation (Aliso Viejo, Calif.),
Mariano Ferraresso, and Amedea Tirelli, and Luciana Ghio, and Paolo Grillo, and Valentina Martina, and Erminio Torresani, and Alberto Edefonti
October 2004, Transplantation,
Mariano Ferraresso, and Amedea Tirelli, and Luciana Ghio, and Paolo Grillo, and Valentina Martina, and Erminio Torresani, and Alberto Edefonti
February 2021, The pharmacogenomics journal,
Mariano Ferraresso, and Amedea Tirelli, and Luciana Ghio, and Paolo Grillo, and Valentina Martina, and Erminio Torresani, and Alberto Edefonti
October 2023, La Tunisie medicale,
Mariano Ferraresso, and Amedea Tirelli, and Luciana Ghio, and Paolo Grillo, and Valentina Martina, and Erminio Torresani, and Alberto Edefonti
January 2018, Pharmacogenomics and personalized medicine,
Mariano Ferraresso, and Amedea Tirelli, and Luciana Ghio, and Paolo Grillo, and Valentina Martina, and Erminio Torresani, and Alberto Edefonti
November 2010, Transplantation proceedings,
Copied contents to your clipboard!