DPP-4 Inhibitors: Renoprotective Potential and Pharmacokinetics in Type 2 Diabetes Mellitus Patients with Renal Impairment
AbstractThe continuously increasing incidence of diabetes worldwide has attracted the attention of the scientific community and driven the development of a novel class of antidiabetic drugs that can be safely and effectively used in diabetic patients. Of particular interest in this context are complications associated with diabetes, such as renal impairment, which is the main cause of high cardiovascular morbidity and mortality in diabetic patients. Intensive control of glucose levels and other risk factors associated with diabetes and metabolic syndrome provides the foundations for both preventing and treating diabetic ne...
Source: European Journal of Drug Metabolism and Pharmacokinetics - August 5, 2019 Category: Drugs & Pharmacology Source Type: research

Effects of Animal Strain, Dose, and Cotreatment with Saikosaponin b 2 on the Pharmacokinetics of Saikosaponin a in Rats
ConclusionsThe pharmacokinetic data for SSa obtained in this study will play an important role in attempts to better understand the fate of SSa in rats and to explore how these saikosaponins are likely to exert their pharmacological effects in vivo. In addition, further research is needed to elucidate the interactions of saikosaponins with metabolic enzymes and transporters in order to account for the phenomena observed in this study. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - July 17, 2019 Category: Drugs & Pharmacology Source Type: research

Clinical Pharmacokinetics of Vancomycin in Critically Ill Children
ConclusionVancomycin dosing strategies in younger children should be revisited, and increased doses should be considered for critically ill children with ARC in order to achieve therapeutic concentrations of AUC0 –24. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - July 12, 2019 Category: Drugs & Pharmacology Source Type: research

Effects of UGT1A1 Polymorphism, Gender and Triglyceride on the Pharmacokinetics of Telmisartan in Chinese Patients with Hypertension: A Population Pharmacokinetic Analysis
ConclusionA PopPK model of telmisartan was established to confirm that UGT1A1 genotype, gender and triglyceride can affect the pharmacokinetics of telmisartan in Chinese patients with hypertension. Our findings can provide relevant pharmacokinetic parameters for further study of telmisartan. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 28, 2019 Category: Drugs & Pharmacology Source Type: research

Comment on: Pharmacokinetics and Safety of Recombinant Human Interleukin-1 Receptor Antagonist GR007 in Healthy Chinese Subjects
(Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 26, 2019 Category: Drugs & Pharmacology Source Type: research

Inhibition of Rat CYP1A2 and CYP2C11 by Honokiol, a Component of Traditional Chinese Medicine
ConclusionThe inhibition of CYP1A2 by honokiol is greater than the inhibition of CYP2C11. The changes in the pharmacokinetics of theophylline and tolbutamide in rats treated with honokiol are due to the inhibition of CYP1A2 and CYP2C11 activity in a dose-dependent manner. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 7, 2019 Category: Drugs & Pharmacology Source Type: research

Vancomycin Pharmacokinetics in Patients with Advanced Cancer Near End of Life
AbstractBackground and ObjectiveThe effect of cancer cachexia on the pharmacokinetics of vancomycin remains unclear. We investigated whether the pharmacokinetics of vancomycin and the risk of kidney injury are altered with the development of cancer cachexia.MethodsA retrospective analysis was conducted using therapeutic drug monitoring data obtained from 86 cancer patients who received vancomycin intravenously for infection. The patients were classified into four groups according to the stage of cachexia defined by international consensus —non-cachexia (n = 26), pre-cachexia (n = 10), cach...
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 1, 2019 Category: Drugs & Pharmacology Source Type: research

Minimal Physiologically Based Pharmacokinetic Model of Intravenously and Orally Administered Delta-9-Tetrahydrocannabinol in Healthy Volunteers
ConclusionIt has recently been reported that the terminal metabolite THC-COOH is active, implying the exposure difference in individuals homozygous for CYP2C9*3 may become therapeutically relevant. Defining the metabolism of THC in humans is important, as it is increasingly being used as a drug to treat various diseases and its recreational use is also rising. We have used NCA, CM, and mPBPK modeling of THC and its metabolites to partially disentangle the complexity of cannabis disposition in humans. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 21, 2019 Category: Drugs & Pharmacology Source Type: research

Dose Escalation Study to Assess the Pharmacokinetic Parameters of a Nano-amorphous Oral Sirolimus Formulation in Healthy Volunteers
ConclusionBased on the pharmacokinetic profiles observed, the nano-amorphous formulation could be a better alternative to Rapamune® for the treatment of mammalian target of rapamycin-responsive malignancies. Therapeutically relevant plasma concentrations and exposures can be achieved by a single 40  mg oral dose. Furthermore, the low variability observed might make therapeutic blood monitoring unnecessary for transplant patients taking sirolimus as an immunosuppressant. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 14, 2019 Category: Drugs & Pharmacology Source Type: research

The Effects of CYP3A5 Genetic Polymorphisms on Serum Tacrolimus Dose-Adjusted Concentrations and Long-Term Prognosis in Chinese Heart Transplantation Recipients
AbstractBackground and ObjectivesEffective management of immunosuppressants is extemely important to improve prognosis of heart transplant recipients.  We aim to investigate the effects of cytochrome P450 (CYP) 3A5 (rs776746) single nucleotide polymorphisms (SNPs) on serum tacrolimus concentrations/doses (C/Ds, ng/mL per mg/kg) and long-term prognosis in Chinese heart transplant recipients.MethodsWe detected the CYP3A5 SNPs of 203 consecutive Chinese heart transplant recipients between August 2005 and July 2012, and 55 of them who received tacrolimus-based immunosuppressive therapy were enrolled in this study. Th...
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 13, 2019 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics and Safety of a Diclofenac Sodium 75  mg/1 mL Solution (Akis ® /Dicloin ® ) Administered as a Single Intravenous Bolus Injection in Healthy Men and Women
ConclusionsDiclofenac sodium 75  mg/1 mL solution administered as a 5-s i.v. bolus was well tolerated. The pharmacokinetic profile, which showed a faster onset and a higher concentration peak than seen for other products and administration routes, suggests a superior analgesic effect. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 10, 2019 Category: Drugs & Pharmacology Source Type: research

Effect of  Dietary Doses of Quercetin on Hepatic Drug Metabolizing Enzymes in Spontaneously Hypertensive Rats
ConclusionThis study demonstrates that dietary doses of QR may offer chemoprevention through stimulation of the endogenous antioxidant systems and inhibition of CYP enzymes involved in bioactivation of procarcinogens. However, modulation of drug metabolizing enzymes by QR could have potential for herb –drug interactions with the possibility of serious complications. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 7, 2019 Category: Drugs & Pharmacology Source Type: research

Current Understanding of the Equivalence Evaluations for In Vitro Tests on Generic Dry Powder Inhaler Drug Products in Japan
This article shows the current understanding and recommendations with respect to in vitro tests, particularly for at least four groups of stages. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 6, 2019 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetics of Voriconazole in Chinese Patients with Hematopoietic Stem Cell Transplantation
ConclusionsA population pharmacokinetic model of voriconazole was successfully established in Chinese hematopoietic stem cell transplantation patients. Based on the final model, CYP2C19*2genotyping coupled with therapeutic drug monitoring seems to be useful to guide voriconazole dosing and to explain subtherapeutic concentrations in clinical practice. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - April 30, 2019 Category: Drugs & Pharmacology Source Type: research

In Vitro Metabolism by Aldehyde Oxidase Leads to Poor Pharmacokinetic Profile in Rats for c-Met Inhibitor MET401
ConclusionsThese results indicate that the main metabolic pathway of MET401 is AO-mediated metabolism, which leads to poor in vivo pharmacokinetic profiles in rodents. The deuterium substitution strategy could be used to reduce AO-mediated metabolism liability. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - April 27, 2019 Category: Drugs & Pharmacology Source Type: research

Predictability of Capillary Blood Spot Toward Venous Whole Blood Sampling for Therapeutic Drug Monitoring of Tacrolimus in Solid Organ Transplant Recipients
The objective of this literature review was to provide a critical evaluation on the feasibility (i.e., accuracy and precision) of DBS for predicting tacrolimus whole blood concentrations in solid organ transplant recipients. A comprehensive systematic literature search using PubMed, Scopus, EMBASE, and Google Scholar was conducted. The primary objective was to extract the bias and precision data from the identified papers. In addition, the collection, storage, and analysis protocols were also summarized. Both adult and pediatric data were included. The reported bias data (primarily based on individual concentrations) in th...
Source: European Journal of Drug Metabolism and Pharmacokinetics - April 22, 2019 Category: Drugs & Pharmacology Source Type: research

Opioids: A Review of Pharmacokinetics and Pharmacodynamics in Neonates, Infants, and Children
AbstractPain management in the pediatric population is complex for many reasons. Mild pain is usually managed quite well with oral acetaminophen or ibuprofen. Situations involving more severe pain often require the use of an opioid, which may be administered by many different routes, depending on clinical necessity. Acute and chronic disease states, as well as the constantly changing maturational process, produce unique challenges at every level of pediatrics in dosing and management of all medications, especially with regard to high-risk opioids. Although there has been significant progress in the understanding of opioid ...
Source: European Journal of Drug Metabolism and Pharmacokinetics - April 22, 2019 Category: Drugs & Pharmacology Source Type: research

In Vitro Study of the Enzymatic and Nonenzymatic Conjugation of Treosulfan with Glutathione
ConclusionTreosulfan does not undergo either spontaneous or enzymatic conjugation with GSH at a noticeable rate. The result indicates that the clearance of treosulfan is independent of glutathioneS-transferase activity, GSH stores, and co-administration of drugs utilizing the GSH metabolic pathway. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - April 16, 2019 Category: Drugs & Pharmacology Source Type: research

Inhibitory Effect of Vonoprazan on the Metabolism of [ 14 C]Prasugrel in Human Liver Microsomes
ConclusionsThe in vitro data show that the pharmacodynamic interaction reported in the literature between vonoprazan and prasugrel is unlikely to be caused by CYP inhibition by vonoprazan. The results were similar to those obtained from the study with clopidogrel. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - April 16, 2019 Category: Drugs & Pharmacology Source Type: research

Clinical and Pharmacokinetic Outcomes of Peak –Trough-Based Versus Trough-Based Vancomycin Therapeutic Drug Monitoring Approaches: A Pragmatic Randomized Controlled Trial
ConclusionMaintenance of target vancomycin exposures and implementation of peak –trough-based vancomycin TDM may improve vancomycin-associated cure rates. Larger scale RCTs are warranted to confirm these findings. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 27, 2019 Category: Drugs & Pharmacology Source Type: research

Comparative Evaluation of Median Versus Youden Index Dichotomization Methods: Exposure –Response Analysis of Mycophenolic Acid and Acyl-Glucuronide Metabolite
ConclusionThe results demonstrated in this analysis suggest that both the Youden index and the median methods provide similar conclusions when dichotomization of a continuous variable is considered. However, confirmation of these conclusions comes from future powered studies that include a larger number of subjects. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 16, 2019 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone (BAY 94-8862) in Individuals with Mild or Moderate Hepatic Impairment
ConclusionThe effects of mild or moderate hepatic impairment on systemic exposure of finerenone are small, consistent with its low hepatic extraction and preponderance of gastrointestinal over hepatic first-pass clearance. Considering the small increases in AUC and the absence of changes inCmax, a dose adaptation does not appear to be warranted in patients with mild or moderate hepatic impairment. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 1, 2019 Category: Drugs & Pharmacology Source Type: research

Inhibitory Mechanisms of Myricetin on Human and Rat Liver Cytochrome P450 Enzymes
ConclusionsIn conclusion, this study indicates that myricetin inhibited CYP3A4/3A2, CYP2C9/2C11, CYP2D6/2D1 and CYP2B1 by various mechanisms with differentKi values. Given that our experiments are established in vitro, further in vivo work is needed to confirm the interaction between myricetin and CYP enzymes, thus providing better guidance for the safe clinical use of myricetin. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 1, 2019 Category: Drugs & Pharmacology Source Type: research

Glucuronidation of d -Luciferin In Vitro: Isoform Selectivity and Kinetics Characterization
ConclusionsUGT1A1, UGT1A3 and UGT1A6 were responsible for 6 ′-O-glucuronidation ofd-luciferin in HLM, while UGT1A1 and UGT1A3 were the major contributors to this biotransformation in HIM. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - February 28, 2019 Category: Drugs & Pharmacology Source Type: research

Fluctuations in Pharmacokinetics Profiles of Monoclonal Antibodies
AbstractMonoclonal antibodies (mAbs) are a group of drugs with predicted slow linear and target-mediated distribution and elimination. Visual inspection of published pharmacokinetic profiles of mAbs frequently reveals plateaus in the distribution phase or an increasing concentration many days after a single intravenous dose. A question which has been left unanswered until now is whether mAbs undergo recirculation mechanisms. If so, then which mechanisms are crucial for the fluctuation in their pharmacokinetics profiles? What is the impact of such mechanisms on mAb absorption, distribution and elimination? Current commentar...
Source: European Journal of Drug Metabolism and Pharmacokinetics - February 27, 2019 Category: Drugs & Pharmacology Source Type: research

Influence of Obesity and Type 2 Diabetes Mellitus on the Pharmacokinetics of Tramadol After Single Oral Dose Administration
ConclusionsNo significant differences were found in the pharmacokinetics of tramadol andO-desmethyltramadol, indicating that the opioid can be administered to overweight, obese and diabetic patients without dosage adjustment. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - February 18, 2019 Category: Drugs & Pharmacology Source Type: research

Enhancing Curcumin Oral Bioavailability Through Nanoformulations
AbstractCurcumin is a promising therapeutic agent that exhibits manifold therapeutic activities. However, it is challenging to study curcumin as it exhibits poor aqueous solubility and low permeability and it is a substrate for P-glycoprotein (P-gp). It is readily metabolized in the body, but many active metabolites of curcumin have been identified that could also be exploited for therapy. Strategies for the oral  bioenhancement of curcumin to leverage the potential of curcumin as a therapeutic molecule are discussed here in light of these challenges. A brief discussion of conventional bioenhancement strategies u...
Source: European Journal of Drug Metabolism and Pharmacokinetics - February 15, 2019 Category: Drugs & Pharmacology Source Type: research

Tacrolimus Variability: A Cause of Donor-Specific Anti-HLA Antibody Formation in Children
ConclusionHigh tacrolimus concentration variability appears to be associated with anti-HLA  antibody formation in pediatric recipients of living-donor renal transplants. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - February 8, 2019 Category: Drugs & Pharmacology Source Type: research

Effect of Gender on the Pharmacokinetics of ON 123300, A Dual Inhibitor of ARK5 and CDK4/6 for the Treatment of Cancer, in Rats
ConclusionsThis investigation demonstrated a significantly lower metabolism of ON 123300 in female rats, which resulted in high systemic exposure. Additional testing is warranted to assess the potential clinical implications of these findings. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 30, 2019 Category: Drugs & Pharmacology Source Type: research

In-Vivo Degradation of DNA-Based Therapeutic BC 007 in Humans
ConclusionFast and full degradation of BC 007, shown by nucleic bases degradation products, is one of the first reports about the fate of a ssDNA product in humans. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 23, 2019 Category: Drugs & Pharmacology Source Type: research

Correction to: Effects of Phenothiazines on Aldehyde Oxidase Activity Towards Aldehydes and N-Heterocycles: an In Vitro and In Silico Study
Unfortunately, the original article was published with error in author names. The author names are corrected here by this correction paper. The  original article has been corrected. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 18, 2019 Category: Drugs & Pharmacology Source Type: research

Clinical Pharmacokinetics of a Lipid-Based Formulation of Risperidone, VAL401: Analysis of a Single Dose in an Open-Label Trial of Late-Stage Cancer Patients
ConclusionsFurther comparisons of the pharmacokinetic parameters of risperidone and 9-hydroxyrisperidone in plasma of patients administered VAL401 and the corresponding parameters obtained from published data for conventionally formulated risperidone provide evidence for altered biological processing of VAL401 as compared to risperidone. The absolute values obtained provide support for future studies of VAL401 as a cancer treatment, as the Cmax demonstrates sufficient exposure to reach the concentrations seen during preclinical anticancer testing, yet the overall exposure to the active moiety supports the use of the safety...
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 9, 2019 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetic Modelling of Pyrazinamide and Pyrazinoic Acid in Patients with Multi-Drug Resistant Tuberculosis
ConclusionsThe developed population pharmacokinetic model adequately described the disposition of pyrazinamide and pyrazinoic acid and can be useful for dose determination of pyrazinamide in patients with MDR-TB. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 8, 2019 Category: Drugs & Pharmacology Source Type: research

Advanced In Vitro HepaRG Culture Systems for Xenobiotic Metabolism and Toxicity Characterization
AbstractSeveral HepaRG three-dimensional (3D) in vitro model systems have been developed to improve the predictability of xenobiotic metabolism and toxicity. In this review, we present a detailed summary and critique of the performance of various HepaRG 3D models compared to the conventional 2D monolayer culture. HepaRG 3D models can be broadly categorized into (1) scaffold-free, (2) scaffold-based, and (3) bioartificial liver (BAL) models. With respect to the scaffold-free configurations, the hanging drop model closely mimics the normal physiological function and metabolic profile of the liver. The micromold model is suit...
Source: European Journal of Drug Metabolism and Pharmacokinetics - December 10, 2018 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetics and Exposure –Response of Lithium Carbonate in Patients Based on Tubular Reabsorption Mechanisms
ConclusionRenal function and urinary pH are important indices in lithium treatment, so the serum concentration of lithium may be predicted based on the renal function and urinary pH. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - December 7, 2018 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetics, Safety and Tolerability of Extended-Release Bupropion and Its Three Metabolites in Chinese Healthy Volunteers
ConclusionsThis was the first pharmacokinetic study for bupropion XL and its active metabolites in the Chinese population. The AUC andCmax of bupropion XL and its three metabolites increased approximately in a dose-proportional manner with an increase from 150  mg to 300 mg. Adverse events were similar to those reported in studies outside China. A population pharmacokinetic model was developed for bupropion XL, with pharmacokinetics of bupropion adequately described by a two-compartment model with first-order absorption and linear elimination plus lag t ime.Trial Registration NumberNCT02698553 (Source: European J...
Source: European Journal of Drug Metabolism and Pharmacokinetics - December 5, 2018 Category: Drugs & Pharmacology Source Type: research

Comparison of the Pharmacokinetic Profiles of Ceftriaxone Used Alone and Combined with Danhong Injection in Old Rats
AbstractBackground and ObjectivesDanhong injection is the most commonly prescribed adjuvant drug applied for the treatment of cardiovascular and cerebrovascular diseases in China. Ceftriaxone is usually prescribed along with Danhong injection to elderly patients with complications. However, the pharmacokinetic interactions between these two medications have not been investigated. The aim of this study was to investigate whether Danhong injection influences the pharmacokinetic profile of ceftriaxone in old rats when these two medications are used in combination.MethodsThe animal experiment protocol was designed according to...
Source: European Journal of Drug Metabolism and Pharmacokinetics - December 3, 2018 Category: Drugs & Pharmacology Source Type: research

Development of a Population Pharmacokinetic Model of Vancomycin and its Application in Chinese Geriatric Patients with Pulmonary Infections
ConclusionA population pharmacokinetic model was established to estimate the pharmacokinetics characteristics of Chinese geriatric patients with pulmonary infections, and this model can be used to develop an initial vancomycin dosing regimen for geriatric patients. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 30, 2018 Category: Drugs & Pharmacology Source Type: research

A Gallbladder-Based Enterohepatic Circulation Model for Pharmacokinetic Studies
ConclusionCaution should be taken when designing clinical studies for drugs that undergo EHC. It may be essential to consider the timing of meals when planning pharmacokinetic studies and defining sampling times. The period over which samples are taken needs to be extended as compared to that traditionally used with other drugs. Future studies that attempt to identify the best sampling strategies in the presence of EHC are needed. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 28, 2018 Category: Drugs & Pharmacology Source Type: research

Conversion from Twice-Daily Prograf ® to Once-Daily Advagraf ® in Multi-ethnic Asian Adult Renal Transplant Recipients With or Without Concomitant Use of Diltiazem: Impact of CYP3A5 and MDR1 Genetic Polymorphisms on Tacrolimus Exposure
ConclusionThe high prevalence of CYP3A5 polymorphism among Asians may lead to a significant reduction in tacrolimus exposure with 1:1 dose conversion of Prograf® to Advagraf®. These results advocate for CYP3A5 determination prior to conversion, and suggest that 1:1.25 conversion should be used for CYP3A5 expressors and 1:1 conversion for other patients. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 23, 2018 Category: Drugs & Pharmacology Source Type: research

A Physiologically Based Pharmacokinetic Model for Optimally Profiling Lamotrigine Disposition and Drug –Drug Interactions
ConclusionsOur developed PBPK lamotrigine profile accurately predicts DDIs and lamotrigine IR/XR formulation disposition in adults and children. This PBPK model will be helpful in designing future DDI studies for co-administration of lamotrigine with other drugs and in designing individualized patient dosing regimens. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 20, 2018 Category: Drugs & Pharmacology Source Type: research

Retraction Note to: Changes of Absorptive and Secretory Transporting System of (1 → 3) β-D-glucan Based on Efflux Transporter in Indomethacin-induced Rat
The Editor-in-Chief has retracted this article [1] based on an investigation by the Ministry of Education, Culture, Sports, Science and Technology, Japan, which found that the article contained overlap with a previously published article by Kalitsky-Szirtes J, et al. [2]. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 14, 2018 Category: Drugs & Pharmacology Source Type: research

Clinical Application of Pharmacokinetics: Basis for Rational Dose Selection in a Critically Ill Patient on Renal Replacement Therapy
ConclusionsSpecific pharmacokinetic software and measuring plasma concentrations of the drugs should be used for calculation of total drug clearance and dose adjustment whenever possible. However, if unavailable, basic pharmacokinetic formulas and principles could be successfully used instead to adjust the dose in critically ill patients on hemodialysis. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 13, 2018 Category: Drugs & Pharmacology Source Type: research

Acknowledgement to Referees
(Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 9, 2018 Category: Drugs & Pharmacology Source Type: research

Hepatic Cytochrome P450 Activity and Nitric Oxide Production During Multiple Ovalbumin Challenges
ConclusionsMultiple OVA challenges, unlike acute sensitization, greatly reduced serum NOx levels. The challenge-suppressed hepatic CYP metabolism was likely related to the increased serum NOx. Serum NOx may be an endogenous marker for CYP metabolism inhibition in type 1 allergic diseases. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 8, 2018 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics and Pharmacodynamics of Cabotegravir, a Long-Acting HIV Integrase Strand Transfer Inhibitor
AbstractAvailable antiretroviral drugs have demonstrated effectiveness in both pre-exposure prophylaxis and treatment of HIV infection. However, some concerns still persist regarding these therapies, mainly related to patient adherence, drug toxicity and dosing convenience. Cabotegravir is a potent integrase strand transfer inhibitor with a chemical structure similar to dolutegravir that is under clinical evaluation both as oral and long-acting injectable (LAI) formulations for both the prevention or treatment of HIV infection. Indeed, preclinical and clinical studies have consistently shown that LAI cabotegravir is readil...
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 1, 2018 Category: Drugs & Pharmacology Source Type: research

Effects of Phenothiazines on Aldehyde Oxidase Activity Towards Aldehydes and N-Heterocycles: an In Vitro and In Silico Study
ConclusionThe five studied phenothiazine drugs showed dual inhibitory effects on AOX activity towards aldehydes and N-heterocycles as two major classes of enzyme substrates. Most of the interactions between the phenothiazine-related drugs and AOX in the binding pocket showed a hydrophobic nature. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 31, 2018 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics and Safety of Recombinant Human Interleukin-1 Receptor Antagonist GR007 in Healthy Chinese Subjects
ConclusionsThe results showed that a single intramuscular injection of 30 –150 mg GR007 had good safety and tolerability in healthy Chinese subjects. The results of the evaluation of the safety and pharmacokinetics of GR007 performed in this study support its use as a repeated daily injection in ongoing clinical trials focusing on patients with cancer. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 31, 2018 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetic Analysis of Immediate-Release Oral Tacrolimus Co-administered with Mycophenolate Mofetil in Corticosteroid-Free Adult Kidney Transplant Recipients
ConclusionWe have developed and internally evaluated a novel population pharmacokinetic model for tacrolimus co-administered with mycophenolate mofetil in corticosteroid-free adult kidney transplant patients. These findings are clinically important and provide further reasons for conducting therapeutic drug monitoring in this specific population. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 30, 2018 Category: Drugs & Pharmacology Source Type: research

In Vitro Assessment of Potential for CYP-Inhibition-Based Drug –Drug Interaction Between Vonoprazan and Clopidogrel
ConclusionsThe body of evidence shows that the pharmacodynamic DDI reported between vonoprazan and clopidogrel is unlikely to be caused by the inhibition of CYP2B6, CYP2C19, or CYP3A4/5 by vonoprazan. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 25, 2018 Category: Drugs & Pharmacology Source Type: research