Pharmacokinetics of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir in Healthy Chinese Subjects and HCV GT1b-Infected Chinese, South Korean and Taiwanese Patients
AbstractBackground/PurposeThe 3 direct-acting antiviral (3D) regimen of ombitasvir/paritaprevir/ritonavir plus dasabuvir has recently been approved in several Asian geographic regions for the treatment of hepatitis C virus (HCV) genotype (GT) 1 infection. The pharmacokinetics of the components of the 3D regimen with or without ribavirin were evaluated in healthy Chinese subjects and HCV GT1b-infected Chinese, South Korean, and Taiwanese patients, with or without cirrhosis, to determine how the drug exposures in Asian populations compare with historical data in Western populations.MethodsParticipants received ombitasvir/par...
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 16, 2018 Category: Drugs & Pharmacology Source Type: research

Bayesian Population Pharmacokinetic Modeling of Eltrombopag in Chronic Hepatitis C Patients
ConclusionsEltrombopag pharmacokinetic behavior was described using population bayesian approach. This model can be applied to optimize eltrombopag dosing in order to reduce the incidence of thrombocytopenia in HCV-infected patient receiving interferon-based therapy. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 14, 2018 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetic Analysis and Model-Based Simulations of Aripiprazole for a 1-Day Initiation Regimen for the Long-Acting Antipsychotic Aripiprazole Lauroxil
ConclusionsModel-based simulations demonstrate that the 1-day initiation regimen is suitable for starting treatment with all AL doses, allowing a window of  ≤ 10 days between initiation and AL administration. ALNCD may also be used to re-establish concentrations associated with therapeutic doses of AL in conjunction with a delayed AL dose. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 11, 2018 Category: Drugs & Pharmacology Source Type: research

Nutritional Status Differentially Alters Cytochrome P450 3A4 (CYP3A4) and Uridine 5 ′-Diphospho-Glucuronosyltransferase (UGT) Mediated Drug Metabolism: Effect of Short-Term Fasting and High Fat Diet on Midazolam Metabolism
This study assesses the effect of two nutritional conditions, short-term fasting, and a short-term high fat diet (HFD) on cytochrome P450 3A4 (CYP3A4) and uridine 5 ′-diphospho-glucuronosyltransferase (UGT) mediated drug metabolism by studying the pharmacokinetics of midazolam and its main metabolites.MethodsIn a randomized-controlled cross-over trial, nine healthy subjects received a single intravenous administration of 0.015  mg/kg midazolam after: (1) an overnight fast (control); (2) 36 h of fasting; and (3) an overnight fast after 3 days of a HFD consisting of 500 ml of cream supplemented to t...
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 6, 2018 Category: Drugs & Pharmacology Source Type: research

Potential Influence of Centrally Acting Herbal Drugs on Transporters at the Blood –Cerebrospinal Fluid Barrier and Blood–Brain Barrier
This article provides an updated review of transporter-mediated mechanisms by which herbal products may theoretically interact with centrally acting medications at the blood–brain barrier and blood–cerebrospinal fluid (CSF) barrier. Further research is required before the true clinical impact of interactions involving modulation of centrally located membrane transporters can be fully understo od. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 1, 2018 Category: Drugs & Pharmacology Source Type: research

Evaluation of Strategies for the Assessment of Drug –Drug Interactions Involving Cytochrome P450 Enzymes
ConclusionsThis study gives a representative overview of current methodologies that can be used to study CYP inhibition. The here presented strategy can be applied as a tool during risk evaluation of CYP-mediated DDIs. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 21, 2018 Category: Drugs & Pharmacology Source Type: research

Evaluation of FOCEI and SAEM Estimation Methods in Population Pharmacokinetic Analysis Using NONMEM ® Across Rich, Medium, and Sparse Sampling Data
ConclusionsFor the classical one- and two-compartment models, FOCEI method exhibited comparable performance similar to SAEM method but with significantly shorter runtimes across rich, medium, and sparse sampling scenarios. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 21, 2018 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics of the Novel, Selective, Non-steroidal Mineralocorticoid Receptor Antagonist Finerenone in Healthy Volunteers: Results from an Absolute Bioavailability Study and Drug –Drug Interaction Studies In Vitro and In Vivo
ConclusionFinerenone is predominantly metabolized by CYP3A4 in the gut wall and liver. Increases in systemic exposure upon concomitant administration of inhibitors of this isoenzyme are predictable and consistent with in vitro data. Inhibition of CYP2C8, the second involved metabolic enzyme, has no relevant effect on finerenone in vivo. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 19, 2018 Category: Drugs & Pharmacology Source Type: research

Effect of Multiple Doses of Omeprazole on the Pharmacokinetics, Safety, and Tolerability of Roxadustat in Healthy Subjects
ConclusionMultiple daily oral doses of 40  mg omeprazole had no significant effect on the pharmacokinetics of a single oral dose of 100 mg roxadustat. Roxadustat was considered safe and well tolerated when administered alone or in combination with multiple daily oral doses of 40 mg omeprazole in healthy subjects. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 11, 2018 Category: Drugs & Pharmacology Source Type: research

Absorption, Distribution, Metabolism, and Excretion of the Novel Helicase-Primase Inhibitor, Amenamevir (ASP2151), in Rodents
ConclusionsThe underlying mechanism of the improved pharmacokinetic profile of amenamevir was linked to an improved absorption ratio (not hepatic availability) compared to acyclovir, and qualitative differences in elimination (slow metabolism of amenamevir vs rapid urinary excretion of acyclovir/valaciclovir). (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 10, 2018 Category: Drugs & Pharmacology Source Type: research

Effect of Naltrexone Hydrochloride on Cytochrome P450 1A2, 2C9, 2D6, and 3A4 Activity in Human Liver Microsomes
ConclusionThese outcomes advocate that there is a great possibility of drug interactions resulting from the concurrent administration of naltrexone hydrochloride with actives that are metabolized by these CYP enzymes, particularly CYP2C9 and CYP2D6. Nevertheless, further clarification is needed through detailed in vivo pharmacokinetic studies. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 9, 2018 Category: Drugs & Pharmacology Source Type: research

In Vitro Monitoring of the Mitochondrial Beta-Oxidation Flux of Palmitic Acid and Investigation of Its Pharmacological Alteration by Therapeutics
ConclusionsThe present work offers a new in vitro screen of changes in mitochondrial beta-oxidation by xenobiotics as well as a model to study the mechanism of this pathway. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 3, 2018 Category: Drugs & Pharmacology Source Type: research

Effect of Gambogenic Acid on Cytochrome P450  1A2, 2B1 and 2E1, and Constitutive Androstane Receptor in Rats
ConclusionsThe obtained results suggest that the CYP1A2 and CYP2E1 enzymes could be induced in rats after treatment with GNA. Therefore, when GNA is administrated with other drugs, potential drug –drug interactions (DDI) mediated by CYP1A2 and CYP2E1 induction should be taken into consideration. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - May 2, 2018 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetic Profiling of Butylidenephthalide and Alisol B in Danggui-Shaoyao-San in Rats
ConclusionsA highly specific, sensitive and rapid HPLC –MS/MS method was developed and applied for the determination of BDPH and ALI in rat plasma. It was found that BDPH and ALI had higher bioavailability in the DSS extract compared with their purified forms. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - April 27, 2018 Category: Drugs & Pharmacology Source Type: research

Impact of the CYP3A5*1 Allele on the Pharmacokinetics of Tacrolimus in Japanese Heart Transplant Patients
ConclusionSimilar concentration –time curves for tacrolimus were obtained in the expresser and non-expresser groups by dose adjustment based on therapeutic drug monitoring. These results demonstrate the importance of the CYP3A5 genotype in tacrolimus dose optimization based on therapeutic drug monitoring after heart transplantat ion. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - April 24, 2018 Category: Drugs & Pharmacology Source Type: research

The Underrated Risks of Tamoxifen Drug Interactions
AbstractTamoxifen is a prodrug, and most of the therapeutic effect in treating breast cancer stems from its metabolite, endoxifen. Since cytochrome P450  (CYP) 2D6 is the most important enzyme in the production of endoxifen, drugs that inhibit CYP2D6 would be expected to reduce tamoxifen efficacy. In addition to drug–drug interactions (DDI) involving CYP2D6, there is growing evidence that enzyme inducers can substantially alter the disposition of endoxifen, reducing tamoxifen efficacy. Although the clinical evidence on the impact of CYP2D6 inhibitors on tamoxifen efficacy is mixed, there were serious flaws in ma...
Source: European Journal of Drug Metabolism and Pharmacokinetics - April 10, 2018 Category: Drugs & Pharmacology Source Type: research

A Population Pharmacokinetic and Pharmacodynamic Analysis of RP5063 Phase 2 Study Data in Patients with Schizophrenia or Schizoaffective Disorder
ConclusionsPharmacokinetics of RP5063 behaved predictably and consistently. Pharmacodynamics were characterized using anEmax model, reflecting total PANSS score as a function of cumulative AUC, that showed high predictability and low variability when correlated with actual observations. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - April 4, 2018 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics of the P-gp Inhibitor Tariquidar in Rats After Intravenous, Oral, and Intraperitoneal Administration
ConclusionThe present findings extend the available information on tariquidar and provide a basis for future studies involving oral administration of this compound. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - April 3, 2018 Category: Drugs & Pharmacology Source Type: research

Influence of Nutritional Status on the Absorption of Polyphyllin I, an Anticancer Candidate from Paris polyphylla  in Rats
ConclusionsThe oral exposure of PPI was enhanced in MN rats, which suggested that nutritional status alters the absorption of PPI, and thus the dosage of PPI should be modified during the treatment of cancer patient with PCM. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 28, 2018 Category: Drugs & Pharmacology Source Type: research

Ocular Pharmacokinetics of 25-Hydroxyvitamin D3 After Weekly Supplementation in Rabbits Using Ultra Performance Liquid Chromatography –Tandem Mass Spectrometer
AbstractBackground and ObjectivesThe protective role of vitamin D supplementation has recently been shown to be present in various ocular inflammatory diseases. The oral supplementation of vitamin D may take time to achieve adequate levels in intraocular fluids. Therefore, the present study was performed to understand the ocular pharmacokinetics of 25-hydroxyvitamin D3 (25D3) in aqueous humor after weekly supplementation of 25D3 in rabbits.MethodsA total of 21 rabbits were fed orally with 25D3 (7.22  µg/kg/week) for 8 weeks and 9th dose was given at the end of 8 weeks. The blood and aqueous humor sampl...
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 26, 2018 Category: Drugs & Pharmacology Source Type: research

Clinical Pharmacokinetics and Drug –Drug Interactions of Elbasvir/Grazoprevir
AbstractElbasvir and grazoprevir, in a fixed-dose combination of 50 and 100  mg, respectively, have received approval to be administered orally once daily, with or without ribavirin, for the treatment of chronic hepatitis C virus (HCV) infections. The absorption characteristics of elbasvir and grazoprevir have been adequately summarized, although differences were observed for grazoprevir (e.g., increased exposure at steady state in patients), but not elbasvir, between healthy and HCV-infected subjects. Inconsistencies with respect to absorption were also reported on the effects of food or acid reducers (famotidine or ...
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 20, 2018 Category: Drugs & Pharmacology Source Type: research

In Vivo Red Blood Cells/Plasma Partition Coefficient of Treosulfan and Its Active Monoepoxide in Rats
ConclusionsTreosulfan and its monoepoxide achieve higher concentrations in plasma than in RBC; therefore, the choice of plasma for bioanalysis is rational as compared to whole blood. The distribution of treosulfan into RBC may be a saturable process at therapeutic concentrations. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 14, 2018 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics and Toxicology of the Neuroprotective e,e,e -Methanofullerene(60)-63-tris Malonic Acid  [C 3 ] in Mice and Primates
ConclusionsThe plasma half-life ofC3 was 8.2 ± 0.2 h, and there was wide tissue distribution, including uptake into brain. The compound was cleared by both hepatic and renal excretion. C3 was quite stable, with minimal metabolism of the compound even after 7  days of treatment. The LD50 in mice was 80  mg/kg for a single intraperitoneal injection, and was>  30 mg/kg/day for sustained administration; therapeutic doses are 1–5 mg/kg/day. For primates, no evidence of renal, hepatic, electrolyte, or hematologic abnormalities were noted, and serial ECGs demonstrated n...
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 8, 2018 Category: Drugs & Pharmacology Source Type: research

Determination of Puquitinib in Human Plasma by HPLC –ESI MS/MS: Application to Pharmacokinetic Study
ConclusionsThe optimized method was successfully applied to the pharmacokinetic profile study in human cancer patient plasma after the oral administration of puquitinib. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 8, 2018 Category: Drugs & Pharmacology Source Type: research

Effects of Ketoconazole and Rifampicin on the Pharmacokinetics of Nintedanib in Healthy Subjects
ConclusionsExposure to nintedanib is increased by co-administration of ketoconazole and decreased by co-administration of rifampicin, likely due to effects on bioavailability of the absorbed fraction.ClinicalTrials.govidentifiers:NCT01679613, NCT01770392. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - March 2, 2018 Category: Drugs & Pharmacology Source Type: research

Pharmacology of Pimasertib, A Selective MEK1/2 Inhibitor
AbstractPimasertib belongs to the growing family of mitogen activated protein kinase (MEK1/2) inhibitors undergoing clinical development for various cancer indications. Since the MEK inhibition in several cell signalling transduction cascades within tumours was considered therapeutically beneficial, number of clinical investigations of pimasertib have been reported. Despite being orally bioavailable in cancer patients, pimasertib undergoes faster clearance with a short elimination half-life. In addition, due to occurrence of toxicity, the development of pimasertib appears to be stalled. Case studies are provided on the pos...
Source: European Journal of Drug Metabolism and Pharmacokinetics - February 27, 2018 Category: Drugs & Pharmacology Source Type: research

Prediction of Human Pharmacokinetics of Ulixertinib, a Novel ERK1/2 Inhibitor from Mice, Rats, and Dogs Pharmacokinetics
ConclusionsThe derived pharmacokinetic parameters (AUC andCmax at 600  mg dose) and simulated plasma concentration–time profiles of ulixertinib in humans were predicted with good confidence by allometric approach. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - February 22, 2018 Category: Drugs & Pharmacology Source Type: research

Metabolism of Rhizoma coptidis in Human Urine by Ultra-High-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry
ConclusionsThe results demonstrated that the metabolic fate ofRhizoma coptidis mainly involved sulfation and glucuronidation in human urine and the glucuronide conjugate M14 (berberrubinen-9-O-glucuronide) might be a pharmacokinetic marker forRhizoma coptidis alkaloids in humans. This study will be helpful to comprehensively understand the metabolic process ofRhizoma coptidis and howRhizoma coptidis shows its pharmacological effects in humans. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - February 15, 2018 Category: Drugs & Pharmacology Source Type: research

Genotyping as a Key Element of Sample Size Optimization in Bioequivalence of Risperidone Tablets
ConclusionsThe test formulation met the Food and Drug Administration guidelines and regulation criteria for bioequivalence. By controlling the genotype, it could actually help reduce the CVw, which may be a feasible method to decrease the sample size for the bioequivalence study of highly variable drugs. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - February 5, 2018 Category: Drugs & Pharmacology Source Type: research

Assessing Propylene Glycol Toxicity in Alcohol Withdrawal Patients Receiving Intravenous Benzodiazepines: A One-Compartment Pharmacokinetic Model
ConclusionIt does not appear that intermittent bolus administration of intravenous benzodiazepines for alcohol withdrawal influenced renal function or anion gap regardless of number of administered doses, amount of PG received, or the estimated PG concentration. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - February 1, 2018 Category: Drugs & Pharmacology Source Type: research

Effects of Human Sulfotransferase 2A1 Genetic Polymorphisms 3 on the Sulfation of Tibolone
ConclusionThe results obtained provided useful information concerning the differential metabolism of tibolone through sulfation in individuals with differentSULT2A1 genotypes. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - February 1, 2018 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics and Safety of Levetiracetam Extended-Release Tablets and Relative Bioavailability Compared with Immediate-Release Tablets in Healthy Chinese Subjects
The objective of this study was to evaluate the pharmacokinetics and safety of levetiracetam extended-release (ER) tablets in healthy Chinese subjects following single and multiple doses.MethodsTwo panels of 34 healthy subjects were enrolled. Trial 1 was a two-way crossover between levetiracetam ER tablets and immediate-release (IR) tablets under fasting conditions. Trial 2 was a four-way crossover single-dose study between levetiracetam ER fasted and ER with food.ResultsIntake of single and multiple levetiracetam ER tablets resulted in a 42.3% lower maximum plasma concentration (Cmax) and a 33.6% lower minimum steady-stat...
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 30, 2018 Category: Drugs & Pharmacology Source Type: research

Drug Delivery and Transport into the Central Circulation: An Example of Zero-Order In vivo Absorption of Rotigotine from a Transdermal Patch Formulation
ConclusionDeconvolution based on rotigotine pharmacokinetic profiles after single- or multiple-dose administration of the once-daily patch demonstrated that in vivo absorption of rotigotine showed constant input through the skin into the central circulation (resembling zero-order kinetics). Continuous absorption through the skin is a basis for stable drug exposure. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 13, 2018 Category: Drugs & Pharmacology Source Type: research

A Simultaneous Mixed-Effects Pharmacokinetic Model for Nefopam, N -desmethylnefopam, and Nefopam N-Oxide in Human Plasma and Urine
ConclusionsA descriptive, robust and predictive parent –metabolite model has been developed using a population mixed-effects approach to characterize the pharmacokinetics of nefopam and its metabolites simultaneously in healthy subjects following oral administration of nefopam. The model may be used for dose selection, analysis of sparse data, identif ication of intrinsic and extrinsic factors, and to model the clinical effects of each analyte. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 5, 2018 Category: Drugs & Pharmacology Source Type: research

CYP Suppression in Human Hepatocytes by Monomethyl Auristatin E, the Payload in Brentuximab Vedotin (Adcetris ® ), is Associated with Microtubule Disruption
ConclusionsMMAE was not a CYP inducer in human hepatocytes. However, it caused a concentration-dependent CYP mRNA suppression and activity. The CYP suppression was associated with microtubule disruption, supporting the reports that intact microtubule architecture is required for CYP regulations. The absence of CYP suppression and microtubule disruption in vitro at the clinical plasma concentrations of MMAE (
Source: European Journal of Drug Metabolism and Pharmacokinetics - December 20, 2017 Category: Drugs & Pharmacology Source Type: research

Vancomycin Dosing and Monitoring: Critical Evaluation of the Current Practice
AbstractAfter more than six decades of its use as the mainstay antibiotic for the treatment of multidrug-resistant Gram-positive bacterial infections, dosing and monitoring of vancomycin therapy have not been optimized. The current vancomycin therapeutic guidelines recommend empiric doses of 15 –20 mg/kg administered by intermittent infusion every 8–12 h in patients with normal kidney function. Additionally, the guidelines recommend trough concentration of 15–20 mg/L as a therapeutic goal for adult patients with severe infections. This review critically discusses the current guide lines con...
Source: European Journal of Drug Metabolism and Pharmacokinetics - December 19, 2017 Category: Drugs & Pharmacology Source Type: research

Prediction of Tumor-to-Plasma Ratios of Basic Compounds in Subcutaneous Xenograft Mouse Models
ConclusionTumor-specific correlation-based regression equations were developed and their applicability was adequately validated across xenografts. These equations could be successfully translated to predict tumor concentrations in order to preclude experimental tumor-Kp determination. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - December 18, 2017 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics, Safety, and Tolerability of Single-Dose Elbasvir in Participants with Hepatic Impairment
ConclusionsThe pharmacokinetics of elbasvir after a single, oral 50-mg dose were not clinically meaningfully altered in non –HCV-infected participants with mild, moderate, or severe hepatic dysfunction. However, since elbasvir is currently available only as part of a fixed-dose combination with grazoprevir, the fixed-dose combination should not be administered to patients with moderate or severe hepatic impairment, due to the significantly increased plasma grazoprevir exposures in those populations. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - December 15, 2017 Category: Drugs & Pharmacology Source Type: research

Association of Whole Blood Tacrolimus Concentrations with Kidney Injury in Heart Transplantation Patients
ConclusionsSupratherapeutic whole-blood tacrolimus trough concentrations are independently associated with the development of AKI in adult heart transplantation patients. More stringent dosing of tacrolimus early after transplantation may be critical in preserving the kidney function. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - December 13, 2017 Category: Drugs & Pharmacology Source Type: research

Modeling Drug Disposition and Drug –Drug Interactions Through Hypothesis-Driven Physiologically Based Pharmacokinetics: a Reversal Translation Perspective
(Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - December 5, 2017 Category: Drugs & Pharmacology Source Type: research

Identification of Uridine 5 ′-Diphosphate-Glucuronosyltransferases Responsible for the Glucuronidation of Mirabegron, a Potent and Selective β 3 -Adrenoceptor Agonist, in Human Liver Microsomes
ConclusionsUGT2B7 is the main catalyst of M11 formation in HLMs. Regarding M13 and M14 formation, UGT1A3 and UGT1A8 are strong candidates for glucuronidation, respectively. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 21, 2017 Category: Drugs & Pharmacology Source Type: research

The Influence of Compatibility of Rhubarb and Radix Scutellariae on the Pharmacokinetics of Anthraquinones and Flavonoids in Rat Plasma
ConclusionsCompatibility of Rhubarb and Radix scutellariae can significantly affect the pharmacokinetic behaviors of characteristic constituents of the two herbs. The cause of these pharmacokinetic differences was further discussed combined with the in vivo ADME (absorption, disposition, metabolism, and excretion) processes of anthraquinones and flavonoids. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 14, 2017 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetic Properties of Saffron and its Active Components
AbstractSaffron as a medicinal plant has many therapeutic effects. Phytochemical studies have reported that saffron is composed of at least four active ingredients which include crocin, crocetin, picrocrocin and safranal. The carotenoids of saffron are sensitive to oxygen, light, heat and enzymatic oxidization. However, regulation of these factors is required for saffron quality. Some pharmacologic effects of saffron and its active compounds include cardioprotective, neuroprotective, memory enhancer, antidepressant and anxiolytic. Among more than 150 chemicals of saffron, the most biologically active components are two car...
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 13, 2017 Category: Drugs & Pharmacology Source Type: research

Physiologically Based Pharmacokinetic Modelling of Cytochrome P450  2C9-Related Tolbutamide Drug Interactions with Sulfaphenazole and Tasisulam
ConclusionsThis optimized tolbutamide PBPK model was verified with two strong CYP2C9 inhibitors and can be applied to the prediction of CYP2C9 interactions for novel inhibitors. Furthermore, this work highlights the utility of mechanistic models in navigating the challenges in conducting clinical pharmacology studies in cancer patients. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 8, 2017 Category: Drugs & Pharmacology Source Type: research

Correction to: Continuous Infusion Versus Intermittent Bolus of Beta-Lactams in Critically Ill Patients with Respiratory Infections: A Systematic Review and Meta-analysis
AbstractUnfortunately,  ≥ was found missing between scores and 20 in conclusion section of the online published article. The original article was corrected. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 7, 2017 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 6, 2017 Category: Drugs & Pharmacology Source Type: research

A Review of the Clinical Pharmacokinetics and Pharmacodynamics of Isavuconazole
AbstractInvasive fungal infections are a major cause of morbidity and mortality, especially for immunocompromised patients. Treatment options are few and most are limited by safety and formulation concerns. Isavuconazole is a new triazole antifungal agent with official indications for the treatment of invasive fungal infections caused byAspergillus andMucormycosis. Its clinical efficacy has been proven in two landmark trials, SECURE and VITAL. This review aims to summarize and evaluate the published literature reporting clinical pharmacokinetic and pharmacodynamic outcome data of isavuconazole in humans. Data from healthy ...
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 4, 2017 Category: Drugs & Pharmacology Source Type: research

Safety, Tolerability and Pharmacokinetics of Oral BI 425809, a Glycine Transporter 1 Inhibitor, in Healthy Male Volunteers: A Partially Randomised, Single-Blind, Placebo-Controlled, First-in-Human Study
ConclusionBI 425809 was generally well-tolerated at doses expected to be clinically relevant. The AE profile suggested possible GlyT1-inhibiting effects.Clinical trial identifierNCT02068690. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 26, 2017 Category: Drugs & Pharmacology Source Type: research

Potential Applications of Gliclazide in Treating Type 1 Diabetes Mellitus: Formulation with Bile Acids and Probiotics
Abstract A major advancement in therapy of type 1 diabetes mellitus (T1DM) is the discovery of new treatment which avoids and even replaces the absolute requirement for injected insulin. The need for multiple drug therapy of comorbidities associated with T1DM increases demand for developing novel therapeutic alternatives with new mechanisms of actions. Compared to other sulphonylurea drugs used in the treatment of type 2 diabetes mellitus, gliclazide exhibits a pleiotropic action outside pancreatic β cells, the so-called extrapancreatic effects, such as antiinflammatory and cellular protective effects, which might be ...
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 16, 2017 Category: Drugs & Pharmacology Source Type: research

Continuous Infusion Versus Intermittent Bolus of Beta-Lactams in Critically Ill Patients with Respiratory Infections: A Systematic Review and Meta-analysis
ConclusionsCI of beta-lactam antibiotics is associated with better cure rates and higher %fT  >  MIC when administered to critically ill patients with respiratory infections, but may be most beneficial in severely ill patients with more resistant Gram-negative bacterial infections. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 12, 2017 Category: Drugs & Pharmacology Source Type: research