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Paediatric clinical pharmacology
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
The CYP3A subfamily consists of at least 4 enzymes: CYP3A4, CYP3A5, CYP3A7 and CYP3A43. CYP3A4/CYP3A5 account for 30 to 40% of total CYP content in the adult liver and intestine. CYP3A4 and CYP3A5 are differentially expressed, but have largely overlapping substrate specificity. CYP3A7 is the main CYP isoform in the human fetal and newborn liver. From the few studies available, it appears that the substrate specificity of CYP3A7 is different from CYP3A4.
Role of Genetic Variability in Breast Cancer Treatment Outcomes
Published in Brian Leyland-Jones, Pharmacogenetics of Breast Cancer, 2020
Kandace L. Amend, Ji-Yeob Choi, Christine B. Ambrosone
CYP3A4 also plays a large role in the metabolism of CP, and the CYP3A4 gene has a number of known variant alleles, including some having functional significance (19). A single base substitution in the 5’ promoter region of the gene (20), present in 9% of European-Americans and 53% of African-Americans (21), with the CYP3A4*1B allele associated with expression levels is 1.4-fold higher than that in common alleles (22). Using enzyme kinetic analyses to evaluate intersample variation in activation of CP by CYP3A and 2B in human liver, both Chang et al. (1993) and Roy et al. (1999) found considerable interindividual differences in CYP3A and CYP2B levels and variation over a wide range in CP hydroxylation (10,23). Variation in CYP3A enzyme levels and expression may be related, in part, to genetic differences or to other chemotherapeutic and natural agents that have been shown to increase CYP3A4 expression (24).
Opioids Analgesics and Antagonists
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
R. Rachana, Tanya Gupta, Saumya Yadav, Manisha Singh
Fentanyl is a potent agonist of μ-opioid receptors and has rapid onset and short duration of action. It has 80 times analgesic potency and respiratory depression as morphine. It is highly lipophilic in nature with strong binding toward plasma proteins (Feierman et al., 1996). Combination of fentanyl with droperidol, produces dissociative analgesia. Its metabolization by CYP3A4 results into the production of various inactive and nontoxic metabolites. High doses of fentanyl cause muscular rigidity (Kubat, 2013).
Assessment of Herb-Drug Interaction Potential of Five Common Species of Licorice and Their Phytochemical Constituents
Published in Journal of Dietary Supplements, 2023
Mona H. Haron, Bharathi Avula, Zulfiqar Ali, Amar G. Chittiboyina, Ikhlas A. Khan, Jing Li, Vivian Wang, Charles Wu, Shabana I. Khan
Our results indicate that licorice root extracts could interfere with the metabolism and clearance of pharmaceutical drugs if consumed concomitantly. Extracts that showed > 2-fold (100%) induction in CYP3A4 and CYP1A2 activity could significantly enhance the metabolism of drugs which are substrates of these enzymes, causing faster clearance which could lead to reduced efficacy that may result in treatment failure (13). As millions of patients with HIV/AIDS are put on treatment with the highly active antiretroviral therapy (HAART), drug interactions have become a major concern for healthcare providers. The use of HAART as a combination of three to four drugs creates a potential for antiretroviral (ARV) drug interactions. This is often complicated by adding additional drugs to treat other ailments such as co-morbidities, chronic conditions, and (or) opportunistic infections. It has been observed that most ARV drug interactions involve drugs that interact with CYP enzymes, especially those that are substrates of CYP3A4 (37).
Cannabidiol drug interaction considerations for prescribers and pharmacists
Published in Expert Review of Clinical Pharmacology, 2022
Myfanwy Graham, Jennifer H Martin, Catherine J Lucas, Bridin Murnion, Jennifer Schneider
Many commonly prescribed drugs are metabolized by the CYP enzymes and may be candidates for drug–drug interactions with cannabidiol. For example, CYP3A4 is involved in the metabolism of about a quarter of all commonly used drugs and inhibition of CYP3A4 may increase serum concentrations of macrolides, calcium channel blockers, benzodiazepines, cyclosporine, sildafenil, antihistamines, haloperidol, antiretrovirals, and some statins. CYP2D6 metabolizes many antidepressants and inhibition has the potential to increase serum concentrations of selective serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotics, beta-blockers, and opioids such as codeine and oxycodone [27]. Some standard drug interaction checking platforms do not distinguish between minor and major CYP metabolic pathways and clinical significance data is not readily available for many potential cannabidiol interactions.
Agrimoniin inhibits the activity of CYP1A2, 2D6, and 3A4 in human liver microsomes
Published in Xenobiotica, 2021
Yanqing Zhou, Qian Xian, Haimin Wei, Jin Zhou, Shengjian Li, Junwei Yang, Xuedong Zhou, Yamei Li
The activity of CYP1A2, 2D6, and 3A4 was observed to be inhibited by agrimoniin, which is responsible for the metabolism of numerous drugs, such as mexiletine, tamoxifen, and amlodipine (Nakajima et al. 1998; Zhu et al. 2014; MacLeod et al. 2017). The drug-drug interaction mediated by CYP3A4 has been widely reported in previous studies. For example, verapamil, a specific inhibitor of CYP3A4, suppressed the pharmacokinetics of oridonin and therefore enhance the system exposure and plasma concentration of oridonin (Liu et al. 2019). The pharmacokinetic interaction between ligustrazine and valsartan, which are commonly used in cardiac and cardiovascular disease, was observed inducing by the induction of CYP3A4 (Liu et al. 2020). A non-competitive manner was suggested in the inhibition of CYP3A4 by agrimoniin in the present results. Although non-competitive inhibition is a reversible process, the inhibition of CYP3A4 by agrimoniin should also attract attention in the co-administration of agrimoniin or Agrimonia pilosa Ledeb with CYP3A4 metabolised drugs. On the other hand, the inhibition of CYP1A2 and 2D6 was demonstrated to be competitive, which might be a result of similar chemical structure and function groups in agrimoniin and corresponding substrates. Although the competitive inhibition could be reversed under certain conditions, the inhibitory effect of agrimoniin on the activity of CYP1A and 2D6 is also a potential risk factor that might induce adverse drug-drug interaction and lead to treatment failure.