Biocomparison Study of Adult and Paediatric Dose Strengths of the Prostacyclin Receptor Agonist Selexipag
ConclusionsPharmacokinetic characteristics of selexipag and its metabolite ACT-333679 following administration of one adult tablet of 200  µg selexipag and four paediatric tablets of 50 µg selexipag were comparable.Trial registrationClinicalTrials.gov identifier: NCT02745860. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 21, 2017 Category: Drugs & Pharmacology Source Type: research

Effects of Glycyrrhizic Acid on the Pharmacokinetics of Pristimerin in Rats and its Potential Mechanism
This study investigates the effects of glycyrrhizic acid on the pharmacokinetics of pristimerin in rats.MethodsThe pharmacokinetics of orally administered pristimerin (2  mg/kg) with or without glycyrrhizic acid pretreatment (at a dose of 100 mg/kg/day for 7 days) were investigated. The plasma concentration of pristimerin was determined using a sensitive and reliable LC–MS/MS method, and the pharmacokinetics profiles were calculated and compared. Additionally, Caco-2 cell transwell model and rat liver microsome incubation experiments were also conducted to investigate its potential mechanism.ResultsThe...
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 19, 2017 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetics of Combined Intravenous and Local Intrathecal Administration of Meropenem in Aneurysm Patients with Suspected Intracranial Infections After Craniotomy
ConclusionThis model incorporates covariates of the creatinine clearance and the drainage volume, and a simple to use dosage regimen table was created to guide clinicians with meropenem dosing. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 14, 2017 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetic Analysis of Bisoprolol in Patients with Stable Coronary Artery Disease
ConclusionsThese findings suggest that one of the causes of clearance of bisoprolol variability in patients with CAD is the difference in renal function. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 2, 2017 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetic Analyses of Lithium: A Systematic Review
ConclusionsModel methodologies in each study are summarized and discussed in this review. For future perspective, a population pharmacokinetic –pharmacodynamic study of lithium is recommended. Moreover, external validation of previously published models should be performed. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 29, 2017 Category: Drugs & Pharmacology Source Type: research

High-Loading Dose of Microencapsulated Gliclazide Formulation Exerted a Hypoglycaemic Effect on Type 1 Diabetic Rats and Incorporation of a Primary Deconjugated Bile Acid, Diminished the Hypoglycaemic Antidiabetic Effect
ConclusionGliclazide microcapsules exerted hypoglycaemic effects in T1DM rats independent of insulin and thus may have potentials in treatment of T1DM. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 25, 2017 Category: Drugs & Pharmacology Source Type: research

Development of Improved Dosing Regimens for Mycophenolate Mofetil Based on Population Pharmacokinetic Analyses in Adults with Lupus Nephritis
ConclusionA ‘tiered’ dosing approach considering patient renal function and CsA co-therapy, rather than a ‘one dose fits all’ approach, would help individualize MMF therapy in adult lupus nephritis patients to ensure more patients have optimal MPA exposure. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 23, 2017 Category: Drugs & Pharmacology Source Type: research

Catechol- O -Methyltransferase and UDP-Glucuronosyltransferases in the Metabolism of Baicalein in Different Species
ConclusionThe detailed kinetic parameters indicated that COMT provide convenience for the next glucuronidation; monkey would be a preferred animal model for the preclinical investigation of baicalein. Importantly, oroxylin A should be reconsidered in evaluating baicalein efficacy against inflammatory diseases. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 23, 2017 Category: Drugs & Pharmacology Source Type: research

Physiologically Based Pharmacokinetic Modelling and Prediction of Metformin Pharmacokinetics in Renal/Hepatic-Impaired Young Adults and Elderly Populations
ConclusionsThe PBPK model adequately characterised the pharmacokinetics of metformin in both young adult and elderly populations. PBPK modelling and simulation can be used as a useful tool to investigate and compare the pharmacokinetics in geriatric populations incorporating various disease conditions. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 23, 2017 Category: Drugs & Pharmacology Source Type: research

Pharmacogenetics of Cannabinoids
AbstractAlthough the application of medical marijuana and cannabinoid drugs is controversial, it is a part of modern-day medicine. The list of diseases in which cannabinoids are promoted as a treatment is constantly expanding. Cases of significant improvement in patients with a very poor prognosis of glioma or epilepsy have already been described. However, the occurrence of side effects is still difficult to estimate, and the current knowledge of the therapeutic effects of cannabinoids is still insufficient. In our opinion, the answers to many questions and concerns regarding the medical use of cannabis can be provided by ...
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 22, 2017 Category: Drugs & Pharmacology Source Type: research

The Role of Drug Metabolites in the Inhibition of Cytochrome P450 Enzymes
AbstractFollowing the drug administration, patients are exposed not only to the parent drug itself, but also to the metabolites generated by drug-metabolizing enzymes. The role of drug metabolites in cytochrome P450 (CYP) inhibition and subsequent drug –drug interactions (DDIs) have recently become a topic of considerable interest and scientific debate. The list of metabolites that were found to significantly contribute to clinically relevant DDIs is constantly being expanded and reported in the literature. New strategies have been developed for better understanding how different metabolites of a drug candidate contr...
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 22, 2017 Category: Drugs & Pharmacology Source Type: research

Enhancement of Curcumin Bioavailability Via the Prodrug Approach: Challenges and Prospects
AbstractCurcumin is a natural product with many interesting pharmacological properties. However, these are offset by the particularly poor biopharmaceutical properties. The oral bioavailability of curcumin in humans is very low, mainly due to low solubility, poor stability, and extensive metabolism. This has led to multiple approaches to improve bioavailability, including administration of curcumin with metabolism inhibitors, formulation into nanoparticles, modification of the curcumin structure, and development of curcumin prodrugs. In this paper, we focus on the pharmacokinetic outcomes of these approaches. Pharmacokinet...
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 10, 2017 Category: Drugs & Pharmacology Source Type: research

Observation of Clinically Relevant Drug Interaction in Chimeric Mice with Humanized Livers: The Case of Valproic Acid and Carbapenem Antibiotics
ConclusionThe DDI of VPA with carbapenems was successfully observed in chimeric mice with humanized livers. The DDI was caused by long-lasting inhibition of hepatic APEH-mediated VPA-G hydrolysis by carbapenems, which strongly supports the APEH-mediated mechanism of the clinical DDI. This is the first example showing the usefulness of chimeric mice with humanized livers for evaluation of a DDI via non-cytochrome P450 enzyme. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - April 26, 2017 Category: Drugs & Pharmacology Source Type: research

Therapeutic Potential and Utility of Elacridar with Respect to P-glycoprotein Inhibition: An Insight from the Published In Vitro, Preclinical and Clinical Studies
AbstractThe occurrence of efflux mechanisms via Permeability-glycoprotein (P-gp) recognized as an important physiological process impedes drug entry or transport across membranes into tissues. In some instances, either low oral bioavailability or lack of brain penetration has been attributed to P-gp mediated efflux activity. Therefore, the objective of development of P-gp inhibitors was to facilitate the attainment of higher drug exposures in tissues. Many third-generation P-gp inhibitors such as elacridar, tariquidar, zosuquidar, etc. have entered clinical development to fulfil the promise. The body of evidence from in vi...
Source: European Journal of Drug Metabolism and Pharmacokinetics - April 3, 2017 Category: Drugs & Pharmacology Source Type: research

Effect of Long-term In Vitro Lithium Exposure on mRNA Levels of Claudin - 3 , CYP1A1 , ABCG2 and GSTM3 Genes in the hCMEC/D3 Human Brain Endothelial Cell Line
ConclusionsOur findings provide new insights into the effects of lithium on some drug transporters and drug-metabolizing enzymes in the BBB that may have consequences in pharmacotherapy. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - April 3, 2017 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetics to Model the Time-Varying Clearance of the PEGylated Asparaginase Oncaspar ® in Children with Acute Lymphoblastic Leukemia
ConclusionThe increase in elimination of PEGylated asparaginase appears to be driven by physicochemical processes that are drug-related. The observed hydrolytically in vitro instability of the drug leads to the hypothesis that this increase in CL might be due to an in vivo hydrolysis of the instable ester bond between PEG and the enzyme combined with an increased elimination of the partly de-PEGylated enzyme (Trial registered atwww.clinicaltrials.gov, NCT0111744). (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 27, 2017 Category: Drugs & Pharmacology Source Type: research

Nicotine Population Pharmacokinetics in Healthy Adult Smokers: A Retrospective Analysis
ConclusionsThe population model was able to describe in different populations the nicotine pharmacokinetics after single product use and after 4  days of ad libitum use of Tobacco Heating System, cigarettes, and of different nicotine replacement therapies with various routes of administration. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 9, 2017 Category: Drugs & Pharmacology Source Type: research

Evaluating the Feasibility of Use of a Foreign Reference Product for Generic Drug Applications: A Retrospective Pilot Study
ConclusionsAlthough this retrospective analysis only included a few drugs and product formulation types, i.e., immediate release, delayed release, and orally disintegrating tablet, these preliminary results suggest that using a foreign reference product in BE studies for generic drug applications could be a feasible approach, but with some restrictions: comparable dissolution profiles, same innovator company, same size, weight, and type of coating as the domestic reference product, etc. Further investigations for other complex formulations are required. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 9, 2017 Category: Drugs & Pharmacology Source Type: research

Hydroxylation Metabolisms of Crassicauline A in Rats Under Toxic Dose
ConclusionsThis work disclosed that crassicauline A is elimilated in rats predominantly by metabolism under toxic dosage and the hydroxylation probably at C-15 might be a potential bioactivation pathway in both rats and human. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 7, 2017 Category: Drugs & Pharmacology Source Type: research

A Two-Period Open-Label, Single-Dose Crossover Study in Healthy Volunteers to Evaluate the Drug –Drug Interaction Between Cimetidine and Inhaled Extrafine CHF 5993
ConclusionsOverall, this study indicates that there is no clinically relevant drug –drug interaction between CHF 5993 and cimetidine. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 7, 2017 Category: Drugs & Pharmacology Source Type: research

Assessment of Drug –Drug Interaction Potential Between Atorvastatin and LCZ696, A Novel Angiotensin Receptor Neprilysin Inhibitor, in Healthy Chinese Male Subjects
ConclusionsWhile atorvastatin had no significant impact on the pharmacokinetics of LCZ696 analytes upon co-administration, theCmax of atorvastatin and its metabolites increased twofold, with a marginal increase in AUC (
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 7, 2017 Category: Drugs & Pharmacology Source Type: research

Effect of Gevokizumab on Interleukin-1 β-Mediated Cytochrome P450 3A4 and Drug Transporter Repression in Cultured Human Hepatocytes
ConclusionGevokizumab attenuates, but not abolishes, IL-1 β-mediated functional repression of CYP3A4 and drug transporters in human hepatocytes, which agrees with the fact that the mAb is considered as a modulator and not a blocker of IL-1β signaling. This attenuation of IL-1β-mediated down-regulation of hepatic detoxifying proteins by gevokizumab may h ave to be evaluated in terms of potential therapeutic protein drug–drug interactions when considering future development and therapeutic uses of this IL-1β neutralizing mAb. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 3, 2017 Category: Drugs & Pharmacology Source Type: research

Antioxidative and Protective Actions of Apigenin in a Paracetamol-Induced Hepatotoxicity Rat Model
ConclusionsThe result of our study indicates that apigenin inhibits the level of lipid peroxidation and significantly increases the enzyme antioxidant defense mechanisms in paracetamol-induced hepatotoxicity in rats. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 1, 2017 Category: Drugs & Pharmacology Source Type: research

Clinical Pharmacokinetic and Pharmacodynamic Profile of Lenvatinib, an Orally Active, Small-Molecule, Multitargeted Tyrosine Kinase Inhibitor
AbstractLenvatinib is a multikinase inhibitor that targets vascular endothelial growth factor (VEGF) receptors 1 –3, fibroblast growth factor receptors 1–4, platelet-derived growth factor receptor-alpha, and RET and KIT proto-oncogenes. Lenvatinib is approved for the treatment of radioiodine-refractory differentiated thyroid cancer in the United States (US), European Union (EU), Canada, Japan, and Switzerl and. It is also approved in combination with everolimus for the treatment of advanced renal cell carcinoma following ≥1 VEGF-targeted treatment in the US and EU. In addition, lenvatinib is under inves...
Source: European Journal of Drug Metabolism and Pharmacokinetics - February 23, 2017 Category: Drugs & Pharmacology Source Type: research

Preclinical Pharmacokinetics and Pharmacodynamics of Pinometostat (EPZ-5676), a First-in-Class, Small Molecule S-Adenosyl Methionine Competitive Inhibitor of DOT1L
AbstractAcute leukemias bearing mixed lineage leukemia (MLL) rearrangements are aggressive diseases characterized by a poor overall prognosis despite multi-agent chemotherapy. Aberrant fusion proteins involving the MLL histone methyltransferase (HMT) lead to recruitment of DOT1L, to a multi-protein complex resulting in aberrant methylation of histone H3 lysine 79 at MLL target genes, and ultimately enhanced expression of critical genes for hematopoietic differentiation, including HOXA9 and MEIS1, and as such defines the established mechanism for leukemogenesis in MLL-rearrangement (MLL-r) leukemias. Pinometostat is a first...
Source: European Journal of Drug Metabolism and Pharmacokinetics - February 21, 2017 Category: Drugs & Pharmacology Source Type: research

Prediction of Tissue-to-Plasma Ratios of Basic Compounds in Mice
ConclusionAll these findings together suggest that mouse specific regression equations developed under controlled experimental conditions could be most appropriate for predicting mouse tissue-Kps for compounds with wide range of volume of distribution. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - February 12, 2017 Category: Drugs & Pharmacology Source Type: research

Characterization of 1-Aminobenzotriazole and Ketoconazole as Novel Inhibitors of Monoamine Oxidase (MAO): An In Vitro Investigation
Conclusions1-Aminobenzotriazole and ketoconazole are characterized as non-competitive inhibitors of mice, rat and human MAO in vitro and the extent of their MAO inhibition potential is species specific. 1-Aminobenzotriazole or ketoconazole can be used as a probe inhibitor in vitro for screening the involvement of MAO-dependent metabolism of new chemical entities (NCE) in early drug discovery. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - February 8, 2017 Category: Drugs & Pharmacology Source Type: research

Systemic Bioavailability and Dose Proportionality of Omega-3 Administered in Free Fatty Acid Form Compared With Ethyl Ester Form: Results of a Phase 1 Study in Healthy Volunteers
ConclusionEPA exposure from OM3-CA and IPE was similar under low-fat dietary conditions, despite OM3-CA containing only approximately half as much EPA as IPE. EPA and DHA exposure from OM3-CA increased proportionally with dose. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 22, 2017 Category: Drugs & Pharmacology Source Type: research

Influence of Sex and Food on the Bioavailability and the R-to-S Conversion of Ketoprofen Stereoisomers in Humans
(Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 18, 2017 Category: Drugs & Pharmacology Source Type: research

Stereoselective Conversion of Ketoprofen in Men Versus Women from Two Different Oral Dosage Formulations: Observations and Introspection of the Pharmacokinetic Data
(Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 18, 2017 Category: Drugs & Pharmacology Source Type: research

Evaluation of the Population Pharmacokinetic Properties of Lidocaine and its Metabolites After Long-Term Multiple Applications of a Lidocaine Plaster in Post-Herpetic Neuralgia Patients
ConclusionsIn conclusion, exposure to lidocaine after the application of the lidocaine medicated plaster was found to be primarily affected by the number of plasters simultaneously applied, i.e., it increased with the number of applied patches, but less than proportionally. No clinically relevant effect of other covariates was found to affect the exposure to lidocaine or its metabolites. As no accumulation was predicted by the model, long-term exposure to lidocaine and its metabolites is not expected to lead to any safety concerns in post-herpetic neuralgia patients. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 11, 2017 Category: Drugs & Pharmacology Source Type: research

On the Molecular Basis Underlying the Metabolism of Tapentadol Through Sulfation
ConclusionTaken together, the results derived from the current study provided a molecular basis underlying the sulfation of tapentadol in humans. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 9, 2017 Category: Drugs & Pharmacology Source Type: research

Effects of Caffeic Acid and Quercetin on In Vitro Permeability, Metabolism and In Vivo Pharmacokinetics of Melatonin in Rats: Potential for Herb-Drug Interaction
AbstractBackground and objectivesMelatonin is a popular dietary supplement and also considered as pharmaceutical product for sleep disorders. Caffeic acid and quercetin are widely distributed in leafy vegetables, fruits, tea extract, and both are used as natural antioxidant. There is an immense concern for health researchers to study the herb/food-drug interactions of melatonin. It is mainly metabolized by CYP1A2 in human so that herbs/foods containing cytochrome P450 (CYP) inhibitors can affect pharmacokinetics of melatonin. By considering pharmacokinetic aspects, the present study was undertaken to evaluate the effects o...
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 8, 2017 Category: Drugs & Pharmacology Source Type: research

A Review of Pharmacogenetics of Antimalarials and Associated Clinical Implications
AbstractGenetic variability in drug-metabolizing enzymes and drug transporters is known to influence the pharmacokinetics of many drugs. Antimalarial drugs are a class of agents known to utilize metabolic and elimination pathways prone to genetic variation. This paper aims to review the genetic variants affecting antimalarial medications and discuss their clinical implications. Data were identified for the genes coding for the cytochrome P450 (CYP) enzymes: CYP2C8, CYP2C19, CYP2A6, CYP2D6, CYP2B6, and the P-glycoprotein drug transporter. Adverse effects of amodiaquine were more common in patients with decreased CYP2C8 meta...
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 8, 2017 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics and Pharmacogenetics of Carbamazepine in Children
AbstractAlthough carbamazepine is one of the oldest anticonvulsant drugs, it is still heavily utilized for treatment of epilepsy in children. The aim of this article was to review the current knowledge about pharmacokinetics and pharmacogenetics of carbamazepine in children. The literature for this review was systematically searched for in the MEDLINE and SCINDEKS databases. Oral bioavailability of carbamazepine in children is about 75 –85%, and it is approximately 75–85% bound to plasma proteins. Apparent volume of distribution is 1.2–1.9 l/kg and total clearance between 0.05 and 0.1 l/h/kg. Ph...
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 6, 2017 Category: Drugs & Pharmacology Source Type: research

Novel Antiretroviral Drugs in Patients with Renal Impairment: Clinical and Pharmacokinetic Considerations
AbstractHighly active antiretroviral therapy (HAART) has dramatically increased the survival of HIV-infected patients from Western countries reducing the incidence of opportunistic infections and AIDS-related malignancies, and improving the patients ’ quality of life compared with the pre-HAART era. HIV is thus now considered in the West as a chronic disease, with the majority of HIV-infected patients successfully reaching an optimal immune and virological outcome a few months after starting HAART. However, this switch from acute to chronic d isease has been accompanied by an increased incidence of chronic kidney dis...
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 6, 2017 Category: Drugs & Pharmacology Source Type: research

Antifibrotic Effects of Carvedilol and Impact of Liver Fibrosis on Carvedilol Pharmacokinetics in a Rat model
ConclusionThe present study provides evidence underlying the antifibrotic effects of carvedilol and enhancement of hepatic efficiency. In addition, the pharmacokinetic parameters of a single dose of carvedilol are altered in liver fibrosis, manifested as delayed clearance. This was attributed to the reduction of both hepatic blood flow and CYP2D6 expression in the liver. Carvedilol co-treatment in CCl4-intoxicated rats for 6  weeks recovered its pharmacokinetic profile, which is mainly attributed to the impact of pharmacodynamic antifibrotic effects of carvedilol on its own kinetics. (Source: European Journal of Drug ...
Source: European Journal of Drug Metabolism and Pharmacokinetics - December 22, 2016 Category: Drugs & Pharmacology Source Type: research

In Vitro Evaluation of Absorption Characteristics of Peramivir for Oral Delivery
ConclusionsThese results revealed that carrier-mediated transports, including OATP1B (organic anion transport 1B) and OCT1 (organic cation transport 1), might be involved in the absorption of peramivir. In conclusion, our results provide insight into the poor oral bioavailability of peramivir. Peramivir can be classified as a BCS-III (high solubility/low permeability) and BDDCS-III high solubility/poor metabolism) drug. The oral bioavailability of peramivir primarily depends on its permeability across cell membranes. Both of passive and active transports are involved in the permeability of peramivir. (Source: European Jour...
Source: European Journal of Drug Metabolism and Pharmacokinetics - December 20, 2016 Category: Drugs & Pharmacology Source Type: research

In Vivo Pharmacokinetics of Puerarin via Different Drug Administration Routes Based on Middle Cerebral Artery Occlusion Model
ConclusionsThe in vivo experiments based on the MCAO model showed that, compared with intravenous route, the bioavailability and brain-targeting of drug were highly improved via intranasal route. In pathological conditions, compared with normal rats, the AUC of puerarin in brain and DTI increased significantly. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - December 6, 2016 Category: Drugs & Pharmacology Source Type: research

Presence of an H + /Quinidine Antiport System in Madin –Darby Canine Kidney Cells
ConclusionsThe present findings suggested that the renal new antiport system is involved in the bidirectional membrane transport of quinidine in MDCK cells. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 25, 2016 Category: Drugs & Pharmacology Source Type: research

Biodistribution and Pharmacokinetic Study of 3,3 ′ Diseleno Dipropionic Acid (DSePA), A Synthetic Radioprotector, in Mice
ConclusionsDSePA has a favorable pharmacokinetic profile which makes it a potentially good candidate for further development as a radioprotective agent. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 23, 2016 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetic Drug Interactions with Panax ginseng
AbstractPanax ginseng is widely used as an adaptogen throughout the world. The major active constituents ofP. ginseng are ginsenosides. Most naturally occurring ginsenosides are deglycosylated by colonic bacteria to intestinal metabolites. Ginsenosides along with these metabolites are widely accepted as being responsible for the pharmacologic activity and drug interaction potential of ginseng. Numerous preclinical studies have assessed the influence of various ginseng components on cytochrome P450 (CYP), glucuronidation, and drug transport activity. Results from these investigations have been largely inconclusive due to th...
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 17, 2016 Category: Drugs & Pharmacology Source Type: research

Physiologically Based Pharmacokinetic (PBPK) Modeling of Pitavastatin and Atorvastatin to Predict Drug-Drug Interactions (DDIs)
ConclusionThrough quantitative assessment of the effect of OATP1B1 genetic polymorphism and inhibitors of transporters and metabolizing enyzmes via PBPK modeling, we confirmed the importance of OATP1B1 in the disposition of these two statins, and explored potential causes for under-prediction of the inhibitory effect of rifampin and cyclosporine. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 16, 2016 Category: Drugs & Pharmacology Source Type: research

Evaluation of In Vitro Cytochrome P450 Inhibition and In Vitro Fate of Structurally Diverse N -Oxide Metabolites: Case Studies with Clozapine, Levofloxacin, Roflumilast, Voriconazole and Zopiclone
ConclusionsClinical DDI potential of specific CYP enzymes needs to be considered arising due to circulatory concentrations of certainN-oxides depending on the dose size and/or frequency of dosing of the respective parent drugs. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 15, 2016 Category: Drugs & Pharmacology Source Type: research

Acknowledgements
(Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 14, 2016 Category: Drugs & Pharmacology Source Type: research

Hepatic Uptake Mechanism of Ophiopogonin D Mediated by Organic Anion Transporting Polypeptides
ConclusionsOverall, this study indicates OATP1B1 in human and oatp1b2 in rats might participate in the hepatic uptake of OPD. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 3, 2016 Category: Drugs & Pharmacology Source Type: research

Liver Perfusion Modifies Gd-DTPA and Gd-BOPTA Hepatocyte Concentrations Through Transfer Clearances Across Sinusoidal Membranes
ConclusionAt a given perfused concentration, portal flow rates modify Gd-BOPTA hepatocyte concentrations, a result important to consider when interpreting liver imaging. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 23, 2016 Category: Drugs & Pharmacology Source Type: research

Identification of Naringin Metabolites in Human Urine and Feces
ConclusionsThe results revealed that naringin underwent extensive phase II metabolism in the human body and yielded an array of conjugated products. This study provided a reference for further clinical studies and in vivo metabolism of other flavonoids.Graphical Abstract (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 14, 2016 Category: Drugs & Pharmacology Source Type: research

Erratum to: Population pharmacokinetic modeling of oxcarbazepine active metabolite in Chinese patients with epilepsy
(Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 13, 2016 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics and Pharmacodynamics of Promising Arginase Inhibitors
AbstractUp-regulation of arginase activity in several chronic disease conditions, including cancer and hypertension, may suggest new targets for treatment. Recently, the number of new arginase inhibitors with promising therapeutic effects for asthma, cancer, hypertension, diabetes  mellitus, and erectile dysfunction has shown a remarkable increase. Arginase inhibitors may be chemical substances, such as boron-based amino acid derivatives,α-difluoromethylornithine (DMFO), andNω-hydroxy-nor-l-arginine (nor-NOHA) or, of plant origin such as sauchinone, salvianolic acid B (SAB), piceatannol-3-O- β-d-gluco...
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 11, 2016 Category: Drugs & Pharmacology Source Type: research