Search results for "pharmacogenetic"
showing 10 items of 92 documents
Molecular docking and pharmacogenomics of vinca alkaloids and their monomeric precursors, vindoline and catharanthine.
2011
International audience; Vinblastine and vincristine are dimeric indole alkaloids derived from (formerly: ). Their monomeric precursor molecules are vindoline and catharanthine. While vinblastine and vincristine are well-known mitotic spindle poisons, not much is known about vindoline and catharanthine. Vindoline and catharanthine showed weak cytotoxicity, while vinblastine, vincristine, and the semisynthetic vindesine and vinorelbine revealed high cytotoxicity towards cancer cells. This may reflect a general biological principle of poisonous plants. Highly toxic compounds are not only active towards predators, but also towards plant tissues. Hence, plants need mechanisms to protect themselv…
The Relevance of Genetic Factors in Tumor Therapy and the Underlying Pharmacogenetic Principles
2017
In the following chapter it is shown that only by the combination of pharmacological and genetic research programs new relevant findings of tumor formation and progression can be gained. This then lead to an improved and individualized therapy of the patients in the area of application.
Pharmacogenomics in psychiatry: from therapeutic drug monitoring to genomic medicine.
2013
Psychiatry is increasingly combining new pharmacogenomic findings with therapeutic drug monitoring (TDM) to improve the safety and efficacy of pharmacotherapy. However, a distinction should be made between “nice to know” and “need to know” pharmacogenomic data because many results are statistically significant in meta-analyses but are not clinically relevant due to their low effect sizes. Some examples will illustrate this integration.
<i>PCSK9</i> rs11591147 R46L Loss-of-Function Variant Protects Against Liver Damage in Individuals with NAFLD
2020
Background and Aims: The proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis, and its inhibition represents an effective therapy to lower LDL-C levels. In this study, we examined the impact of PCSK9 rs11591147 loss-of-function (LOF) variant on liver damage in a multicenter collection of patients at risk of nonalcoholic steatohepatitis (NASH), in clinical samples and experimental models. Methods: We considered 1,874 consecutive individuals at risk of NASH as determined by histology. The SNP rs11591147, encoding for the p.R46L variant of PCSK9, was genotyped by TaqMan assays. We also evaluated 1) PCSK9 mRNA hepatic expression in human liver, and 2…
Pharmacogenetics and Pharmacotherapy of Military Personnel Suffering from Post-traumatic Stress Disorder
2017
Background Posttraumatic stress disorder (PTSD) is a severe problem among soldiers with combating experience difficult to treat. The pathogenesis is still not fully understood at the psychological level. Therefore, genetic research became a focus of interest. The identification of single nucleotide polymorphisms (SNPs) may help to predict, which persons are at high risk to develop PTSD as a starting point to develop novel targeted drugs for treatment. Methods We conducted a systematic review on SNPs in genes related to PTSD pathology and development of targeted pharmacological treatment options based on PubMed database searches. We focused on clinical trials with military personnel. Results…
Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017
2017
AbstractTherapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug…
Pharmacogenetics in Neuroblastoma: What Can Already Be Clinically Implemented and What Is Coming Next?
2021
Pharmacogenetics is one of the cornerstones of Personalized Precision Medicine that needs to be implemented in the routine of our patients’ clinical management in order to tailor their therapies as much as possible, with the aim of maximizing efficacy and minimizing toxicity. This is of great importance, especially in pediatric cancer and even more in complex malignancies such as neuroblastoma, where the rates of therapeutic success are still below those of many other types of tumors. The studies are mainly focused on germline genetic variants and in the present review, state of the art is presented: which are the variants that have a level of evidence high enough to be implemented in the c…
Problem solving in psychopharmacotherapy using pharmacokinetic and pharmacogenetic tests
2007
Many problems such as non-response, pharmacokinetic interactions with clinical consequences and adverse effects (pharmacovigilance) may be observed in patients submitted to psychopharmacotherapy. These risks are increased in patients belonging to the category of “special populations”: elderly patients, children and adolescents, patients with a genetic particularity of metabolism or suffering from somatic or psychic comorbidities. Pharmacokinetic and pharmacogenetic tests are useful to solve problems in psychopharmacotherapy and thus improve efficacy and safety. Therapeutic drug monitoring (TDM) is particularly recommended in situations presented above and in patients who are non-compliant. …
F9 missense mutations impairing factor IX activation are associated with pleiotropic plasma phenotypes.
2022
Background Circulating dysfunctional factor IX (FIX) might modulate distribution of infused FIX in hemophilia B (HB) patients. Recurrent substitutions at FIX activation sites (R191-R226, >300 patients) are associated with variable FIX activity and antigen (FIXag) levels. Objectives To investigate the (1) expression of a complete panel of missense mutations at FIX activation sites and (2) contribution of F9 genotypes on the FIX pharmacokinetics (PK). Methods We checked FIX activity and antigen and activity assays in plasma and after recombinant expression of FIX variants and performed an analysis of infused FIX PK parameters in patients (n = 30), mostly enrolled in the F9 Genotype and PK HB …
Clinical implications ofCYP3Apolymorphisms
2006
Due to their enormous substrate spectrum CYP3A4, -3A5 and -3A7 constitute the most important drug-metabolising enzyme subfamily in humans. CYP3As are expressed predominantly, but not exclusively, in the liver and intestine, where they participate in the metabolism of 45 - 60% of currently used drugs and many other compounds such as steroids and carcinogens. CYP3A expression and activity vary interindividually due to a combination of genetic and nongenetic factors such as hormone and health status, and the impact of environmental stimuli. Over the past several years, genetic determinants have been identified for much of the variable expression of CYP3A5 and -3A7, but not for CYP3A4. Using th…