- The effects of transcranial direct current stimulation compared to standard bupropion for the treatment of tobacco dependence: A randomized sham-controlled trial. [Journal Article]
- EPEur Psychiatry 2019 May 14; 60:41-48
- CONCLUSIONS: The 12-week tDCS had a clinically good therapeutic effect on smoking cessation and its dependency. It may be a substitute for bupropion treatment.
- Modulation of CYP450 activities in patients with type 2 diabetes. [Journal Article]
- CPClin Pharmacol Ther 2019 May 17
- We conducted a comprehensive in vivo study evaluating the influence of type 2 diabetes (T2D) on major CYP450 activities. These activities were assessed in 38 T2D and 35 non-T2D subjects after a singl…
We conducted a comprehensive in vivo study evaluating the influence of type 2 diabetes (T2D) on major CYP450 activities. These activities were assessed in 38 T2D and 35 non-T2D subjects after a single oral administration of a cocktail of probe drugs: 100mg caffeine (CYP1A2), 100mg bupropion (CYP2B6), 250mg tolbutamide (CYP2C9), 20mg omeprazole (CYP2C19), 30mg dextromethorphan (CYP2D6), 2mg midazolam (CYP3As), and 250mg chlorzoxazone (alone) (CYP2E1). Mean metabolic activity for CYP2C19, CYP2B6 and CYP3A were decreased in T2D subjects by about 46%, 45% and 38% (p<0.01), respectively. CYP1A2 and CYP2C9 activities appeared slightly increased in diabetic subjects and no difference was observed for CYP2D6 or CYP2E1 activities. Several covariables such as inflammatory markers (IL-1β, IL-6, IFN-γ and TNF-∝), genotypes, diabetes- and demographic-related factors were considered in our analyses. Our results indicate that low chronic inflammatory status associated with T2D modulates CYP450 activities in an isoform specific manner. This article is protected by copyright. All rights reserved.
- Identifying Smoking Status and Smoking Cessation Using a Data Linkage Between the Kentucky Cancer Registry and Health Claims Data. [Journal Article]
- JCJCO Clin Cancer Inform 2019; 3:1-8
- CONCLUSIONS: Augmenting KCR data with medical claims data increased capture of smoking status and use of smoking-cessation modalities. Cancer registries interested in exploring smoking status to influence treatment and research activities could consider a similar approach, particularly if their registry does not capture smoking status for a majority of patients.
- Update on drug safety evaluation of naltrexone/bupropion for the treatment of obesity. [Journal Article]
- EOExpert Opin Drug Saf 2019 May 16; :1-4
- Patient Characteristics Associated with Receipt of Prescription Weight-Management Medications Among Veterans Participating in MOVE! [Journal Article]
- OObesity (Silver Spring) 2019 May 15
- CONCLUSIONS: Of patients engaged in MOVE! in the VHA, 1.1% received WMM. WMM are underutilized among veterans. Additional research is needed to understand barriers to incorporating WMM into comprehensive obesity treatment plans.
- Pharmacokinetic interactions study between carvedilol and some antidepressants in rat liver microsomes - a comparative study. [Journal Article]
- MPMed Pharm Rep 2019; 92(2):158-164
- CONCLUSIONS: The co-administration of tested antidepressants led to a significant alteration of carvedilol's metabolism in vitro. CYP2D6 inhibition is the main pharmacokinetic mechanism that can explain these drug-drug interactions, with possible clinical implications.
- Bupropion, a possible antidepressant without negative effects on alcohol relapse. [Journal Article]
- ENEur Neuropsychopharmacol 2019 May 04
- CONCLUSIONS: our results suggest that SSRIs can negatively impact alcohol consumption in relapse while SNDRIs have no effects. The observed increase in alcohol consumption are accompanied by functional alterations in the glutamatergic and endocannabinoid systems. This finding could open new strategies for the treatment of depression in patients with alcohol use disorders.
- Cardiovascular Risk Reduction Associated with Pharmacological Weight Loss: A Meta-Analysis. [Journal Article]
- IJInt J Clin Res Trials 2019; 4(1)
- CONCLUSIONS: Our study demonstrated the favorable and significant effect of pharmacological weight reduction strategies on weight loss, blood pressure reduction, glycemic control (A1C reduction), and CVD mortality.While weight loss without pharmacological means has been shown to reduce CVD risk, the mechanism by which weight loss medications impact CVD risk reduction could be a direct effect of these agents or merely an effect of weight reduction itself. Weight loss has been noted to modify risk factors via improving insulin sensitivity, reducing inflammation, decreasing blood pressure and modifying the lipid profile, In addition, the mechanism of action of the medications are not directly anti-inflammatory, and do not directly modify insulin sensitivity, blood pressure or the lipid profile. Thus, it is most likely that the benefit on cardiovascular disease from these therapies is via weight reduction and not direct medication effect.Given the limited efficacy of the lifestyle modification on sustained weight loss and the surgical risk and limited availability of bariatric surgical options. Our data suggests pharmacological weight loss therapy may be a valuable treatment option to reduce CVD risk in obese patients. Further research is needed to clarify the effects these therapies on overall mortality and evaluate the mechanisms by which these medications reduce CVD risk factors and mortality.
- Medical Genetics Summaries: Deutetrabenazine Therapy and CYP2D6 Genotype [BOOK]
- BOOKNational Center for Biotechnology Information (US): Bethesda (MD)
- Deutetrabenazine (brand name Austedo) is used to treat chorea associated with Huntington disease (HD) and tardive dyskinesia (TD). Both HD and TD are types of involuntary movement disorders. The reco…
Deutetrabenazine (brand name Austedo) is used to treat chorea associated with Huntington disease (HD) and tardive dyskinesia (TD). Both HD and TD are types of involuntary movement disorders. The recommended starting dose is 6 mg once daily for individuals with HD and 12 mg per day (6 mg twice daily) for individuals with TD. The maximum recommended daily dosage for both conditions is 48 mg (24 mg, twice daily). The active metabolites of deutetrabenazine are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). The VMAT2 protein transports the uptake of monoamines, such as dopamine, into the nerve terminal. The inhibition of VMAT2 leads to a depletion of pre-synaptic dopamine and reduces the amount of dopamine realized when that neuron fires. This is thought to lead to fewer abnormal, involuntary movements. The CYP2D6 enzyme converts the active metabolites of deutetrabenazine to minor, reduced activity metabolites. Individuals who have no CYP2D6 activity (“CYP2D6 poor metabolizers”) are likely to have a 3- to 4-fold increased exposure to active metabolites, compared with normal metabolizers, following the recommended standard doses of deutetrabenazine. The 2018 FDA-approved drug label for deutetrabenazine states that the daily dose of deutetrabenazine should not exceed 36 mg (maximum single dose of 18 mg) for individuals who are CYP2D6 poor metabolizers or concurrently taking a strong CYP2D6 inhibitor (e.g., quinidine, antidepressants such as paroxetine, fluoxetine, and bupropion) (Table 1). In addition, the drug label cautions that tetrabenazine, a closely related VMAT2 inhibitor, causes QT prolongation. Therefore, a clinically relevant QT prolongation may occur in some individuals treated with deutetrabenazine who are CYP2D6 poor metabolizers or are co-administered a strong CYP2D6 inhibitor (1).
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- The effect of chronic kidney disease on CYP2B expression and activity in male Wistar rats. [Journal Article]
- PRPharmacol Res Perspect 2019; 7(3):e00475
- Chronic kidney disease (CKD) is characterized by progressive reduction in kidney function over time. CKD affects greater than 10% of the population and its incidence is on the rise due to the growing…
Chronic kidney disease (CKD) is characterized by progressive reduction in kidney function over time. CKD affects greater than 10% of the population and its incidence is on the rise due to the growing prevalence of its risk factors. Previous studies demonstrated CKD alters nonrenal clearance of drugs in addition to reducing renal clearance. We assessed the function and expression of hepatic CYP2B enzymes using a rat model of CKD. CKD was induced in Wistar rats by supplementing their chow with adenine and confirmed through the detection of elevated uremic toxins in plasma. Liver enzymes AST and ALT were unchanged by the adenine diet. Bupropion was used as a probe substrate for hepatic CYP2B function using rat liver microsomes. The resulting metabolite, hydroxy-bupropion, and bupropion were quantified by ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry. Level of mRNA and protein were determined by RT-PCR and Western blot, respectively. The results of our study demonstrate that CYP2B1 is downregulated in a rat model of CKD. CYP2B1 mRNA level was significantly decreased (88%, P < 0.001) in CKD relative to control. Similarly, maximal enzymatic velocity (V max) for CYP2B was decreased by 46% in CKD relative to control (P < 0.0001). Previous studies involving patients with CKD demonstrated altered bupropion pharmacokinetics compared to control. Hence, our results suggest that these alterations may be mediated by attenuated CYP2B hepatic metabolism. This finding may partially explain the alterations in pharmacokinetics and nonrenal drug clearance frequently observed in patients with CKD.