Impact of Obesity and Bariatric Surgery on Metabolic Enzymes and P-Glycoprotein Activity Using the Geneva Cocktail Approach.

The inter-individual variability of CYP450s enzyme activity may be reduced by comparing the effects of bariatric surgery on CYP-mediated drug elimination in comparable patients before and after surgery. The current research will use a low-dose phenotyping cocktail to simultaneously evaluate the activities of six CYP isoforms and P-gp. The results showed that following weight reduction after surgery, the activity of all enzymes increased compared to the obese period, which was statistically significant in the case of CYP3A, CYP2B6, CYP2C9, and CYP1A2.

Expression, Purification, and Biological Evaluation of XTEN-GCSF in a Neutropenic Rat Model.

Granulocyte colony-stimulating factor (GCSF) stimulates the proliferation of neutrophils but it has low serum half-life. Therefore, the present study was done to investigate the effect of XTENylation on biological activity, pharmacokinetics, and pharmacodynamics of GCSF in a neutropenic rat model. XTEN tag was genetically fused to the N-terminal region of GCSF-encoding gene fragment and subcloned into pET28a expression vector.

Evaluation of important human CYP450 isoforms and P-glycoprotein phenotype changes and genotype in type 2 diabetic patients, before and after intensifying treatment regimen using Geneva cocktail.

The present study evaluates the influence of type 2 diabetes (T2D) on important CYP450 (CYP) isoforms and P-glycoprotein (Pgp) transporter activities before and 3 months after an intensifying treatment regimen involving 40 patients. Results have been compared with 21 non-T2D healthy participants (the control group). CYPs and Pgp activities were assessed after administering the Geneva cocktail.

Variations in the Frequencies of Polymorphisms in the CYP450s Genes in Eight Major Ethnicities of Iran: A Review of the Human Data.

Genetic polymorphisms in cytochrome P450 genes can cause variation in metabolism. Thus, single nucleotide variants significantly impact drug pharmacokinetics, toxicity factors, and efficacy and safety of medicines. The distribution of CYP450 alleles varies drastically across ethnicities, with significant implications for personalized medicine and the healthcare system.

Fundamentals and Applications of Isolated Perfused Lung (IPL) Model in the Development of Pulmonary Drug Delivery.

Estimating parameters such as pulmonary drug disposition and deposited dose, as well as determining the influence of pulmonary pharmacokinetics (PK) on drug efficacy and safety, are critical factors for the development of inhaled drug products and help to achieve a better understanding of the drugs' fate in the lungs. Pulmonary disposition and PK have remained poorly understood due to the difficulty to access pulmonary fluids, compared to other biological fluids, such as plasma, for direct or surrogate measurement of the concentration of the active compounds and their metabolites in the lung. The use of the isolated perfused lung model (IPL) has become more common, and it is considered a useful tool to increase understanding in this area since it offers the possibility of controlling the administration and easier sampling of perfusate and lavage fluid.

Extension of human GCSF serum half-life by the fusion of albumin binding domain.

Granulocyte colony stimulating factor (GCSF) can decrease mortality of patients undergo chemotherapy through increasing neutrophil counts. Many strategies have been developed to improve its blood circulating time. Albumin binding domain (ABD) was genetically fused to N-terminal end of GCSF encoding sequence and expressed as cytoplasmic inclusion bodies within Escherichia coli.

Evaluation of phenoconversion phenomenon in obese patients: the effects of bariatric surgery on the CYP450 activity "a protocol for a case-control pharmacokinetic study".

Personalized therapy suggests the appropriate drug at the right dose for the first time through genotype-based individualized therapy, instead of prescribing medicines by the traditional one-size-fits-all manner, thereby claiming that it will make medicines safer and more effective. Accordingly, polymorphisms of drug metabolizing enzymes (DMEs), which induce inter-individual variability in the pharmacokinetics of a drug, have attracted great interest in the context of personalized medicine. Obesity is one of the most common chronic diseases in the world, including Iran, and the prevalence is increasing according to predictions.

Frequency of Important CYP450 Enzyme Gene Polymorphisms in the Iranian Population in Comparison with Other Major Populations: A Comprehensive Review of the Human Data.

Genetic polymorphisms in cytochrome P450 genes can cause alteration in metabolic activity of clinically important medicines. Thus, single nucleotide variants (SNVs) and copy number variations (CNVs) in CYP genes are leading factors of drug pharmacokinetics and toxicity and form pharmacogenetics biomarkers for drug dosing, efficacy, and safety. The distribution of cytochrome P450 alleles differs significantly between populations with important implications for personalized drug therapy and healthcare programs.

SN38 loaded nanostructured lipid carriers (NLCs); preparation and in vitro evaluations against glioblastoma.

SN38 is the active metabolite of irinotecan with 1000-fold greater cytotoxicity compared to the parent drug. Despite the potential, its application as a drug is still seriously limited due to its stability concerns and low solubility in acceptable pharmaceutical solvents. To address these drawbacks here nanostructured lipid carrier (NLC) containing SN38 was prepared and its cytotoxicity against U87MG glioblastoma cell line was investigated.

Can combination therapy with insulin and metformin improve metabolic function of the liver, in type I diabetic patients? An animal model study on CYP2D1 activity.

Introduction: Changes in hepatic clearance and CYP2D1 activity after combination therapy with insulin and metformin in type-1 diabetes and insulin administration in type-2 diabetes was assessed in an animal model.

Methods: Ten male Wistar rats were divided into two groups. Seven days after induction of diabetes, in treatment groups, type-1 diabetic rats received insulin plus metformin, and type-2 diabetic rats received insulin daily for 14 days.

Evaluation of hepatic CYP2D1 activity and hepatic clearance in type I and type II diabetic rat models, before and after treatment with insulin and metformin.

Introduction: Conversion in the metabolism of drugs occurs in diabetes mellitus. Considering the importance of metabolic enzymes' activities on the efficacy and safety of medicines, the changes in liver enzymatic activity of CYP2D1 and its related hepatic clearance, by using Dextromethorphan as probe in the animal model of type I and type II diabetes, before and after treatment, was assessed in this study.

Methods: Male Wistar rats were randomly divided into 6 groups.

Evaluating the effect of type 2 diabetes mellitus on CYP450 enzymes and P-gp activities, before and after glycemic control: A protocol for a case-control pharmacokinetic study.

Cytochrome P450s (CYP450) family is one of the most critical factors in the metabolism process. Hence, the present study aims to characterize the activity of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5, and P-glycoprotein (P-gp) pump in patients with type 2 diabetes (T2DM). This characterization was performed before and after good glycemic control versus non-diabetic subjects following the administration of a substrate probe drug cocktail.

Pharmacokinetic changes of tramadol in rats with hepatotoxicity induced by ethanol and acetaminophen in perfused rat liver model.

Tramadol is an opioid agonist with activation monoaminergic properties. It can be administered orally, rectally, intravenously, or intramuscularly as a centrally acting analgesic. Liver injury can lead to changes in the metabolism of tramadol.

Fabrication of a novel aptasensor based on three-dimensional reduced graphene oxide/polyaniline/gold nanoparticle composite as a novel platform for high sensitive and specific cocaine detection.

In the present research, we have developed a novel label free aptasensor based on screen printed carbon electrode (SPCE) modified with three-dimensional magnetic reduced graphene oxide(3D-MRGO)/polyaniline(PA)/gold nanoparticle(AuNP) nanocomposite for impedimetric determination of cocaine. To achieve this goal, a specific thiolated cocaine aptamer was immobilized onto the surface of synthesized nanocomposite. The signaling mechanism of the proposed aptasensor was based on increase in the [Fe(CN)] charge transfer resistance (R) as an electrochemical probe in the presence of target analyte.

Changes in CYP2D enzyme activity following induction of type 2 diabetes, and administration of cinnamon and metformin: an experimental animal study.

1. Alterations in the activity of hepatic cytochrome P-450 isoenzymes result in changes in the pharmacokinetic behavior of drugs. This study was designed to explore the impact of type II diabetes, metformin and cinnamon on the activity of CYP2D isoenzyme.

Inhibition of mirtazapine metabolism by Ecstasy (MDMA) in isolated perfused rat liver model.

Background: Nowadays MDMA (3,4-methylendioxymethamphetamine), known as ecstasy, is widely abused among the youth because of euphoria induction in acute exposure. However, abusers are predisposed to depression in chronic consumption of this illicit compound. Mirtazapine (MRZ), an antidepressant agent, may be prescribed in MDMA-induced depression.

A disposition kinetic study of Tramadol in bile duct ligated rats in perfused rat liver model.

Tramadol hydrochloride is a centrally acting synthetic opioid analgesic drug and is used to treat chronic pain. In this study, the effects of Bile Duct Ligation (BDL) on the pharmacokinetics of tramadol in a liver recirculating perfusion system of male rats were used. Twenty-four Wistar male rats were randomly divided into four groups: control, sham and two weeks BDL and four weeks BDL.

Modified fractal iron oxide magnetic nanostructure: A novel and high performance platform for redox protein immobilization, direct electrochemistry and bioelectrocatalysis application.

A novel biosensing platform based on fractal-pattern of iron oxides magnetic nanostructures (FIOMNs) and mixed hemi/ad-micelle of sodium dodecyl sulfate (SDS) was designed for the magnetic immobilization of hemoglobin (Hb) at a screen printed carbon electrode (SPCE). The FIOMNs was successfully synthesized through hydrothermal approach and characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM) and X-ray diffraction (XRD). In order to provide guidelines for the mixed hemi/ad-micelle formation, zeta-potential isotherms were investigated.

Determination of MDMA and its three metabolites in the rat perfused liver.

3,4-Methylenedioxymethamphetamine (MDMA) is one of the most commonly abused illicit drugs in the world. We developed a rapid and simple high-performance liquid chromatography with a fluorescence (FL) detector method to determine MDMA and its metabolites, such as 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxyamphetamine (HMA) and its main unstable metabolite 3,4-dihydroxymethamphetamine (HHMA) besides the internal standards, in a perfusion medium. The separation of analytes was performed at 25°C on a Chromolith® C18 (100 × 4.

Study of the pharmacokinetic changes of Tramadol in diabetic rats.

Background: Besides the pathological states, diabetes mellitus may also alter the hepatic biotransformation of pharmaceutical agents. It is advantageous to understand the effect of diabetes on the pharmacokinetic of drugs. The objective of this study was to define the pharmacokinetic changes of tramadol and its main metabolites after in vivo intraperitoneal administration and ex vivo perfused liver study in diabetic rat model.

Determination of the role of calcium on instability of neurotoxic metabolite of ecstasy by HPTLC-mass.

Background: Ecstasy is one of the popular illicit drugs in the world and its usage has been recently increased in Iran. This compound can destroy the serotonergic neurons and produces cognitive and psychopathology diseases. 3,4-dihydroxymethamphetamine (HHMA) which is the main metabolite of this compound, seems to be responsible for this effect.

Investigation on different levels of in vitro-in vivo correlation: gemfibrozil immediate release capsule.

Gemfibrozil is a practically water-insoluble, high-dose drug. It represents a typical drug with dissolution rate controlled bioavailability. The aim of this study was to select a dissolution condition for gemfibrozil immediate release capsules, resulting in the best in vitro/in vivo correlation (IVIVC).

An improved HPLC method for rapid quantitation of diazepam and its major metabolites in human plasma.

A rapid and specific HPLC method was developed and validated for simultaneous determination of diazepam and its main active metabolites, desmethyldiazepam, oxazepam and temazepam in human plasma. Plasma samples were extracted using toluene. HPLC system included a Chromolith Performance RP-18e 100 mm x 4.

A disposition kinetic study of tramadol in rat perfused liver.

A recirculated perfusion system was used to investigate the metabolism of tramadol, an analgesic agent, in the isolated perfused rat liver. Tramadol was added to the perfusion medium at a concentration of 300 ng/ml, and the perfusate samples were collected for 180 min. The concentration of tramadol and its three main metabolites O-desmethyltramadol (M1) and N-desmethyltramadol (M2) and N,O-didesmethyltramadol (M5) were determined in perfusate samples by a rapid HPLC method.