CYP3A4 metabolism gender

AIMS: To develop a semi-mechanistic hepatic compartmental model to predict the effects of rifampicin, a known inducer of CYP3A4 enzyme, on the metabolism of five drugs, in the hope of informing dose adjustments to avoid potential drug-drug interactions. METHODS: A search was conducted for DDI studies on the interactions between rifampicin and CYP substrates that met specific criteria, including the availability of plasma concentration-time profiles, physical and absorption parameters, pharmacokinetic parameters, and the use of healthy subjects at therapeutic doses...

INTRODUCTION: Treatment with cannabis extracts for a variety of diseases has gained popularity. However, differences in herb-drug interaction potential of extracts from different plant sources are poorly understood. In this study, we provide a characterization of cannabis extracts prepared from four cannabis chemotypes and an in vitro assessment of their Cytochrome P450 (CYP)-mediated herb-drug interaction profiles. METHODS: Plant extracts were either commercially obtained or prepared using ethanol as solvent, followed by overnight decarboxylation in a reflux condenser system...

Itraconazole is a triazole antifungal agent with highly variable pharmacokinetics, with not yet fully identified factors as the source of this variability. Our study aimed to examine the influence of body mass index, gender, and age on the first dose pharmacokinetics of itraconazole in healthy subjects, using pharmacokinetic modeling, non-compartmental versus compartmental ones. A total of 114 itraconazole and hydroxy-itraconazole sets of plasma concentrations of healthy subjects of both genders, determined using a validated liquid chromatographic method with mass spectrometric detection (LC-MS), were obtained for pharmacokinetic analyses performed by the computer program Kinetica 5® ...

Lurbinectedin is a novel and potent selective inhibitor of active transcription of protein-coding genes, triggering apoptosis of cancerous cells, which has been approved for the treatment of patients with metastatic small-cell lung cancer with disease progression on or after platinum-based chemotherapy. Different studies aimed at exploring the disposition and metabolism of lurbinectedin were performed in vitro and in vivo (by intravenous administration of lurbinectedin). Low blood cell partitioning for lurbinectedin in rat, nonhuman primate (NHP) and human was determined as 23...

Atremorine is a novel bioproduct obtained by nondenaturing biotechnological processes from a genetic species of Vicia faba. Atremorine is a potent dopamine (DA) enhancer with powerful effects on the neuronal dopaminergic system, acting as a neuroprotective agent in Parkinson's disease (PD). Over 97% of PD patients respond to a single dose of Atremorine (5 g, p.o.) 1 h after administration. This response is gender-, time-, dose-, and genotype-dependent, with optimal doses ranging from 5 to 20 g/day, depending upon disease severity and concomitant medication...

From the start of the use of psychoactive prescription medications in the 1950s, physicians reported paradoxical adverse reactions, ranging from newly developing depressions to an increase in existing mood disorders, and extremely violent and bizarre acts of suicide and homicide. It is hypothesized that interactions between the drugs and the enzymes that are primarily responsible for their metabolism (cytochrome P450s) could cause these reactions. In this research, we evaluate statistical associations between CYP450 variant alleles, psychoactive medication, and acts of violence...

OBJECTIVES: Hydroxychloroquine (HCQ) has been used as an off label for the management of coronavirus disease (Covid-19) infection with other drugs. However, different genetic variants can affect the metabolism of HCQ leading to inter-individual differences in its efficacy. In this study, we investigated the effects of variants in CYP2D6, CYP3A4 and CYP3A5 on the risk of Covid-19 infection among patients receiving HCQ for controlling rheumatoid arthritis (RA). METHODS: A total of 60 patients were genotyped for CYP2D6*2XN, CYP2D6*4, CYP3A4*1B and CYP3A5*2...

Prader-Willi syndrome (PWS) is associated with co-morbid psychiatric symptoms (disruptive behavior, anxiety, mood disorders, and psychosis) often requiring psychotropic medications. In this clinical case series of 35 patients with PWS, pharmacogenetic testing was obtained to determine allele frequencies predicting variations in activity of cytochrome (CYP) P450 drug metabolizing enzymes 2D6, 2B6, 2C19, 2C9, 3A4, and 1A2. Results were deidentified, collated, and analyzed by PWS genetic subtype: 14 deletion (DEL), 16 maternal uniparental disomy (UPD) and 5 DNA-methylation positive unspecified molecular subtype (PWS Unspec)...

OBJECTIVES: ATP-binding cassette (ABC) drug efflux transporters and drug metabolic enzymes could reduce antiretroviral (ARV) concentrations in HIV target cells. The testis has been demonstrated to be a sanctuary site, displaying suboptimal ARV concentrations and persistent HIV infection. Therefore, we compared the expression and function of ABC transporters and metabolic enzymes in CD4 and CD8 T cells isolated from human testis and peripheral blood mononuclear cells (PBMCs), and assessed their expression in circulating naïve and memory CD4 T-cell phenotypes...

Buprenorphine is a partial μ-opioid agonist widely used for opioid maintenance therapy (OMT). It is mainly metabolized to pharmacologically active norbuprenorphine by the cytochrome P450 (CYP) isozyme 3A4. This may give rise to drug-drug interactions under combinations with inhibitors or inducers of CYP3A4. Cannabis is a potential inhibitor of CYP3A4, and there is a large degree of concomitant cannabis use among OMT patients. We performed a retrospective analysis on liver healthy OMT patients substituted with buprenorphine, either with (n = 15) or without (n = 17) concomitant use of cannabis...

Background: Cytochrome P450 3A4 ( CYP3A4 ) regulates pharmacokinetic and pharmacodynamic interactions during the process of drug absorption and metabolism, suggesting CYP3A4 plays an important role in drug addiction. However, the association between CYP3A4 polymorphisms and drug addiction risk is still not clear. Methods: This case-control study included 504 drug addicts and 501 healthy controls from Xi'an, China. Four single nucleotide polymorphisms (SNP) in CYP3A4 (rs3735451, rs4646440, rs35564277, and rs4646437) were genotyped by Agena MassARRAY platform...

RATIONALE: Although methadone maintenance treatment (MMT) has long been used for opioid addiction, our knowledge on its pharmacokinetics is still limited. OBJECTIVES: We aimed to investigate effects of age, gender, and various co-medications on methadone serum concentration-to-dose ratio (CDR) in a naturalistic setting. METHODS: In total, 4425 routine serum methadone concentrations obtained from 1691 MMT patients in the period October 1999 to July 2017 were included...

BACKGROUND: Lung cancer is a malignant tumor disease with high morbidity and high mortality. The non-small cell lung cancer (NSCLC) is the most common type, among them, lung squamous cell carcinoma own special pathological type and specific treatment, is a subtype of non-small cell lung cancer and can be divided into peripheral type and central type according to clinical phenotype. This study explores the differences in gene levels and their potential values based on clinical differences between central and peripheral in lung squamous cell carcinoma...

AIM: Erlotinib is a tyrosine kinase inhibitor used in the treatment of non-small cell lung cancer highly metabolized by the cytochrome P450 (CYP) 3A. Hence, the CYP3A4 activity might be a useful predictor for erlotinib pharmacokinetics in personalized medicine. The effect of erlotinib on CYP3A activity was therefore studied in non-small cell lung cancer patients. METHODS: The study included 32 patients scheduled for erlotinib monotherapy. CYP3A activity was assessed using quinine as a probe before and during erlotinib treatment...

BACKGROUND: Women diagnosed with breast cancer frequently seek complementary and alternative (CAM) treatment options that can help to cope with their disease and the side effects of conventional cancer therapy. Especially in Europe, breast cancer patients use herbal products containing mistletoe (Viscum album L.). The oldest and one of the most prescribed conventional drugs for the treatment of estrogen receptor positive breast cancer is tamoxifen. Aside from positive clinical experience with the combination of tamoxifen and mistletoe, little is known about possible herb-drug interactions (HDIs) between the two products...

GOALS: Although all children with nephrotic syndrome (NS) have similar biochemical abnormalities and clinical manifestations, they seem to have variable grades of steroid responsiveness and patterns of disease relapse. Therefore, this study aimed to examine whether steroid metabolism-related genetic polymorphisms, which are responsible for drug elimination, play a role for steroid response in children with NS. METHODS: The study population consisted of 53 children with idiopathic NS [45 steroid sensitive (SS) and 8 steroid resistant (SR) nephrotic patients] and 22 healthy children as the control group...

Objective Since the majority of direct-acting antivirals (DAAs) that are used in the treatment of hepatitis C virus (HCV) infection are mainly metabolized by CYP3A4, it is hypothesized that inter-individual differences in CYP3A4 activity may be associated with the bioavailability of these agents. Methods The level of serum 4β-hydroxycholesterol (4βHC), a surrogate marker of CYP3A4 activity, was determined by LC-MS/MS in samples obtained from patients with HCV infection (CHCs) as well as healthy control subjects (CTLs)...

BACKGROUND: Several studies found differences in tacrolimus whole blood trough levels (C0) or area-under-the curve (AUC) between the twice-daily (Tac-BID) and once-daily (Tac-OD) formulations given to kidney transplant recipients at equal doses. As C0 is widely used as a surrogate of the AUC for individual dose adjustment, this study investigated the correlation and proportionality between C0 and the 24h-AUC, depending on the formulation, time post-transplantation, pharmacogenetics traits and other individual characteristics...

Phase I and phase II biochemical reactions involved in the biotransformation pathways of tolvaptan were characterized by LC-MS-based techniques and in vitro models to identify the most appropriate marker(s) of intake. The effects of physiological and non-physiological factors on the metabolic profile of tolvaptan were also evaluated. In vitro approaches were based on the use of pooled human liver microsomes and recombinant isoforms of cytochrome P450 and uridine diphospho glucuronosyl-transferase. Sample preparation included liquid/liquid extraction at neutral pH with tert-butyl methyl-ether...

AIM: 4β-Hydroxycholesterol (4βOHC) is sensitive towards induction or inhibition of CYP3A4, but its potential usefulness as a dosing biomarker remains to be demonstrated. The aim of this study was to investigate the correlation between 4βOHC levels and steady-state concentrations (Css) of quetiapine, a CYP3A4 substrate with high presystemic metabolism, in psychiatric patients. METHODS: Serum samples from 151 patients treated with quetiapine as immediate release (IR; n = 98) or slow release (XR; n = 53) tablets were included for analysis of 4βOHC...