OPEN ACCESS ARTICLE – Pharmacokinetics, Pharmacodynamics and Pharmacogenetics of Tacrolimus in Kidney Transplantation

Journal Name: Current Drug Metabolism

Author(s): Meng Yu, Mouze Liu, Wei Zhang, Yingzi Ming*.

 

 

 

Graphical Abstract:

 

Abstract:

Background: Tacrolimus (Tac, or FK506), a calcineurin inhibitor (CNI), is the first-line immunosuppressant which consists of the footstone as immunosuppressive regimens in kidney transplantation. However, the drug toxicity and the significant differences of pharmacokinetics (PK) and pharmacodynamics (PD) among individuals are hidden troubles for clinical application. Recently, emerging evidences of Tac pharmacogenetics (PG) regarding drug absorption, metabolism, disposition, excretion and response are discovered for better understanding of this drug.

Method: We reviewed the published articles regarding the Tac PG and its effects on PK and PD in kidney transplantation. In addition, we summarized information on polygenic algorithms.

Results: The polymorphism of genes encoding metabolic enzymes and transporters related to Tac were largely investigated, but the results were inconsistent. In addition to CYP3A4, CYP3A5 and P-gp (also known as ABCB1), single nucleotide polymorphisms (SNPs) might also affect the PK and PD parameters of Tac.

Conclusion: The correlation between Tac PK, PD and PG is very complex. Although many factors need to be verified, it is envisaged that thorough understanding of PG may assist clinicians to predict the optimal starting dosage, help adjust the maintenance regimen, as well as identify high risk patients for adverse effects or drug inefficacy.

READ MORE HERE: http://www.eurekaselect.com/159463

PRESS RELEASE – Pharmacogenetics of angiotensin-converting enzyme inhibitors for Alzheimer’s disease

This article by Dr. Fabricio Ferreira de Oliveira et al. is published in Current Alzheimer Research, Volume 15, Issue 4, 2018

The angiotensin-converting enzyme is an amyloid-ß-degrading enzyme. While angiotensin-converting enzyme inhibitors could increase amyloid-ß accumulation, they might also slow cognitive decline by way of cholinergic effects, by increasing brain substance P and boosting the activity of neprilysin, and by modulating glucose homeostasis and augmenting the secretion of adipokines to enhance insulin sensitivity in patients with Alzheimer’s disease dementia. In this study from São Paulo, Brazil, we aimed to investigate whether ACE polymorphisms rs1800764 and rs4291 are associated with cognitive and functional change in patients with Alzheimer’s disease dementia, while also taking APOE haplotypes and anti-hypertensive treatment with angiotensin-converting enzyme inhibitors into account for stratification. Overall, 193 consecutive patients with late-onset Alzheimer’s disease dementia were screened with cognitive tests, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic correlations were estimated for one year, considering APOE and ACE genotypes and haplotypes, and treatment with angiotensin-converting enzyme inhibitors. Almost 94% of all patients used cholinesterase inhibitors, whereas 155 had arterial hypertension, and 124 used angiotensin-converting enzyme inhibitors. No functional impacts were found regarding any genotypes or pharmacological treatment. Either for carriers of ACE haplotypes that included rs1800764 — T and rs4291 — A, or for APOE4- carriers of rs1800764 — T or rs4291 — T, angiotensin-converting enzyme inhibitors slowed cognitive decline independently of blood pressure variations, possibly by way of central and peripheral effects. APOE4+ carriers were not responsive to treatment with angiotensin-converting enzyme inhibitors. In conclusion, angiotensin-converting enzyme inhibitors may slow cognitive decline for patients with Alzheimer’s disease dementia, more remarkably for APOE4- carriers of specific ACE genotypes. Future trials should prospectively compare angiotensin-converting enzyme inhibitors according to their brain-penetrating properties since the start of anti-hypertensive therapy, with measurements of cerebrospinal fluid and serum levels and activity of the angiotensin-converting enzyme, as well as genetic profiles and neuroimaging parameters.

For more information on this research, please visit: http://www.eurekaselect.com/156397/article

 

Podcast: Thiopurine Biotransformation and Pharmacological Effects

Author: Dr. Marco Pelin

For article details, visit: http://benthamscience.com/journals/current-drug-metabolism/volume/17/issue/6/page/542/

Subscribe our YouTube channelhttp://bit.ly/1lr0czy

Bentham Open Access Article

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The article entitled “A 30-years Review on Pharmacokinetics of Antibiotics: Is the Right Time for Pharmacogenetics?” in the journal Current Drug Metabolism, 2014, 15, 581-598, is now open for all to view and access.

Download the complete article here: http://bit.ly/1vlXVKT
For journal information, please visit: http://bit.ly/1qUXoAe

 

Special Thematic Issue of Current Drug Metabolism

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Tentative Outline
Special Issue for Current Drug Metabolism

Guest Editor: Jose A.G. Agúndez

CLINICAL USE OF BIOMARKERS IN DRUG METABOLISM
AND ADVERSE DRUG REACTIONS

Aims & Scope:
In spite of the large effort and the huge amount of pharmacogenomics information available in
the literature, until now only a small number of pharmacogenomics biomarkers are being used routinely
in clinical practice. Several barriers to implementing the use of pharmacogenomics testing exist. This
special issue will focus on developments, barriers and regulatory issues regarding clinical use of
biomarkers. These will include (but not limited to) new procedures for the identification of biomarkers
(NG sequencing, microRNAs, exploitation of the 1000 genomes project); Barriers to implementing the
use of pharmacogenomics testing; Non-genetic biomarkers of drug response; Identification and validation
of Gene/drug pairs; Refinement in the predictive capacity of conventional pharmacogenomic tests;
Development of clinical practice recommendations or guidelines for the clinical use of biomarkers related
to drug response.

Keywords:
Biomarkers, pharmacogenetics, drug response, gene/drug pairs, barriers, refinement, bioinformatics,
guidelines.

Subtopics:
Barriers in the clinical use of biomarkers.
Pharmacogenomic tests: gene-drug pairs.
Refinement if the predictive capacity of biomarkers.
New challenges in the use of pharmacogenomic biomarkers.
New computational approaches for the exploitation of genetic data.

Schedule:

Manuscript submission deadline: July 2013

Peer Review Due: August 2013

Revision Due: September 2013

Notification of acceptance by the Guest Editor: October 2013

Final manuscripts due: October 2013

 

For details, please visit: http://benthamscience.com/journal/special-issues.php?journalID=cdm

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