Pharmacokinetics-based Chronotherapy

2022 ◽  
Vol 23 ◽  
Author(s):  
Danyi Lu ◽  
Zhigang Wang ◽  
Baojian Wu
Keyword(s):  
Current Knowledge ◽  
Drug Metabolizing Enzymes ◽  
Time Dependency ◽  
Key Factors ◽  
Metabolizing Enzymes ◽  
Diurnal Rhythmicity

Abstract: Dosing time-dependency of pharmacokinetics (or chronopharmacokinetics) has been long recognized. Studies in recent years have revealed that diurnal rhythmicity in expression of drug-metabolizing enzymes and transporters (DMETs) are key factors determining chronopharmacokinetics. In this article, we briefly summarize current knowledge with respect to circadian mechanisms of DMETs and discuss how rhythmic DMETs are translated to drug chronoeffects. More importantly, we present our perspectives on pharmacokinetics-based chronotherapy.

scholarly journals Pharmacogenetics of Carbamazepine and Valproate: Focus on Polymorphisms of Drug Metabolizing Enzymes and Transporters

2021 ◽  
Vol 14 (3) ◽  
pp. 204
Author(s):  
Teresa Iannaccone ◽  
Carmine Sellitto ◽  
Valentina Manzo ◽  
Francesca Colucci ◽  
Valentina Giudice ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Drug Response ◽  
Current Knowledge ◽  
Individual Variability ◽  
Mood Stabilizers ◽  
Drug Metabolizing Enzymes ◽  
Efficacy And Safety ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Metabolizing Enzymes ◽  
Drug Pharmacokinetics

Pharmacogenomics can identify polymorphisms in genes involved in drug pharmacokinetics and pharmacodynamics determining differences in efficacy and safety and causing inter-individual variability in drug response. Therefore, pharmacogenomics can help clinicians in optimizing therapy based on patient’s genotype, also in psychiatric and neurological settings. However, pharmacogenetic screenings for psychotropic drugs are not routinely employed in diagnosis and monitoring of patients treated with mood stabilizers, such as carbamazepine and valproate, because their benefit in clinical practice is still controversial. In this review, we summarize the current knowledge on pharmacogenetic biomarkers of these anticonvulsant drugs.

Analysis of the Potential Association of Drug-Metabolizing Enzymes CYP2C9*3 and CYP2C19*3 Gene Variations With Type 2 Diabetes: A Case-Control Study

2020 ◽  
Vol 21 (14) ◽  
pp. 1152-1160
Author(s):  
Imadeldin Elfaki ◽  
Rashid Mir ◽  
Faisel Mohammed Abu-Duhier ◽  
Chandan Kumar Jha ◽  
Adel Ibrahim Ahmad Al-Alawy ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Antiplatelet Drug ◽  
Drug Metabolizing Enzymes ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Metabolizing Enzymes ◽  
Specific Pcr ◽  
Increased Risk ◽  
Different Populations

Background:: Cytochrome P450s (CYPs) are drug-metabolizing enzymes catalyzing the metabolism of about 75% of drug in clinical use. CYP2C9 represents 20% CYP proteins in liver cells and is a crucial member of CYPs superfamily. CYP2C19 metabolizes very important drugs such as antiulcer drug omeprazole, the antiplatelet drug clopidogrel and anticonvulsant mephenytoin. Single nucleotide polymorphisms (SNPs) of CYP genes have been associated with unexpected drug reactions and diseases in different populations. Objective:: We examined the associations of CYP2C9*3 (rs1057910) and CYP2C19*3 (rs4986893) with T2D in Saudi population. Methods:: We used the allele-specific PCR (AS-PCR) and DNA sequencing in 111 cases and 104 controls for rs1057910, and in 119 cases and 110 controls for rs4986893. Results:: It is indicated that the genotype distribution of rs1057910 in cases and controls were not significantly different (P=0.0001). The genotypes of rs1057910 were not associated with type 2 diabetes (T2D) (P>0.05). Whereas the genotype distribution of rs4986893 in cases and controls was significantly different (P=0.049). The AA genotype of rs4986893 may be associated in increased risk to T2D with OR=17.25 (2.06-143.8), RR=6.14(0.96-39.20), P=0.008. Conclusion:: The CYP2C9*3 (rs1057910) may not be associated with T2D, while CYP2C19*3 (rs4986893) is probably associated with T2D. These findings need to be validated in follow-up studies with larger sample sizes and different populations.

scholarly journals Chirality Matters: Biological Activity of Optically Pure Silybin and Its Congeners

2021 ◽  
Vol 22 (15) ◽  
pp. 7885
Author(s):  
Vladimír Křen
Keyword(s):  
Neurological Diseases ◽  
Biological Effects ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes ◽  
Biological Targets ◽  
Molecular Effects ◽  
Anisotropic Systems ◽  
Specific Activities ◽  
Optically Pure

This review focuses on the specific biological effects of optically pure silymarin flavo-nolignans, mainly silybins A and B, isosilybins A and B, silychristins A and B, and their 2,3-dehydro derivatives. The chirality of these flavonolignans is also discussed in terms of their analysis, preparative separation and chemical reactions. We demonstrated the specific activities of the respective diastereomers of flavonolignans and also the enantiomers of their 2,3-dehydro derivatives in the 3D anisotropic systems typically represented by biological systems. In vivo, silymarin flavonolignans do not act as redox antioxidants, but they play a role as specific ligands of biological targets, according to the “lock-and-key” concept. Estrogenic, antidiabetic, anticancer, antiviral, and antiparasitic effects have been demonstrated in optically pure flavonolignans. Potential application of pure flavonolignans has also been shown in cardiovascular and neurological diseases. Inhibition of drug-metabolizing enzymes and modulation of multidrug resistance activity by these compounds are discussed in detail. The future of “silymarin applications” lies in the use of optically pure components that can be applied directly or used as valuable lead structures, and in the exploration of their true molecular effects.

Sign in / Sign up

Export Citation Format

Share Document