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

Population Pharmacokinetic Modeling of Azithromycin Eyedrops in Tears Following Single-Dose Topical Administration in Healthy Volunteers
ConclusionA proposed linear two-compartment PopPK model of azithromycin eyedrops was found to be effective at describing the disposition of azithromycin in tears after ocular instillation. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 24, 2018 Category: Drugs & Pharmacology Source Type: research

Mechanistic Assessment of the Effect of Omeprazole on the In Vivo Pharmacokinetics of Itraconazole in Healthy Volunteers
ConclusionUnlike SUBA itraconazole, which requires basic pH for itraconazole release, the omeprazole-induced pH-mediated reduction in Sporanox dissolution overrides any increased exposure from the drug –drug interaction at hepatic metabolizing enzymes or efflux transporters. The model presented here is the most complete quantitative description of the pharmacokinetics of itraconazole and hydroxyitraconazole currently available. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 16, 2018 Category: Drugs & Pharmacology Source Type: research

Improved Oral Absorption of Quercetin from Quercetin Phytosome ®, a New Delivery System Based on Food Grade Lecithin
ConclusionsA more soluble formulation of quercetin based on lecithin, Quercetin Phytosome, has recently been developed, and was found to facilitate the attainment of very high plasma levels of quercetin —up to 20 times more than usually obtained following a dose of quercetin—when the novel formulation was administered orally in human volunteers, and it did not have any notable side effects. These results suggest that Quercetin Phytosome allows the oral administration of quercetin in a safe and bioavailable manner, thus facilitating the effective utilization of this natural compound to treat various human diseas...
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 16, 2018 Category: Drugs & Pharmacology Source Type: research

Clinical Pharmacokinetics and Pharmacodynamics of Delafloxacin
This article provides a balanced and comprehensive systematic critique of the literature in order to provide an up-to-date summary of its clinical pharmacology. Oral delafloxacin is rapidly absorbed and exhibits comparable exposure characteristics (300  mg intravenous versus 450 mg oral) between the two formulations, allowing easy transition from intravenous to oral therapy. The bioavailability is high (60–70%) and absorption is not affected by food intake, although further studies are required under clinically relevant conditions. Delafloxaci n is primarily excreted renally (thus requiring renal dose adjus...
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 15, 2018 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics Comparison, Intestinal Absorption and Acute Toxicity Assessment of a Novel Water-Soluble Astragaloside IV Derivative (Astragalosidic Acid, LS-102)
ConclusionsOral LS-102 produced a pharmacokinetic profile different from AGS IV with higher bioavailability, while the toxic tolerance was similar to previous estimates. Thus, we speculated that LS-102 might provide better clinical efficacy and be a potential candidate for the new drug development of Radix Astragali. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 12, 2018 Category: Drugs & Pharmacology Source Type: research

Effect of 95% Ethanol Khat Extract and Cathinone on in vitro Human Recombinant Cytochrome P450 (CYP) 2C9, CYP2D6, and CYP3A4 Activity
ConclusionKhat-drug interactions are possible due to administration of clinical drugs metabolized by CYP2C9/CYP2D6/CYP3A4 together with khat chewing. Further in vivo studies are required to confirm our findings and identify the causative constituents of these inhibitory effects. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 10, 2018 Category: Drugs & Pharmacology Source Type: research

Comparison of In Vitro Stereoselective Metabolism of Bupropion in Human, Monkey, Rat, and Mouse Liver Microsomes
ConclusionThe results demonstrate that phase I metabolism in monkeys best approximates that observed in humans, and support the preferred use of this species to investigate possible pharmacokinetic factors that influence the CNS disposition of bupropion and contribute to its high intersubject variability. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 8, 2018 Category: Drugs & Pharmacology Source Type: research

Clinical Pharmacokinetics of Second-Generation Triazoles for the Treatment of Invasive Aspergillosis and Candidiasis
AbstractSecond-generation triazoles were developed in response to the quest for more efficacious and safer therapeutic options for the treatment of severe systemic aspergillosis and candidiasis. These agents include voriconazole, posaconazole, isavuconazole, and ravuconazole. The aim of this review was to present and compare the pharmacokinetic characteristics of second-generation triazoles for the treatment of invasive  aspergillosis and candidiasis, emphasizing their clinical implications. The MEDLINE, Scopus, EBSCO, Google Scholar, and SCIndeks databases were searched using advanced search options, including the na...
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 3, 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 - October 1, 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 - October 1, 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 - October 1, 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 - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

Animal Pharmacokinetic/Pharmacodynamic Studies (APPS) Reporting Guidelines
AbstractAnimal pharmacokinetic/pharmacodynamic studies are commonly used to provide meaningful preclinical information that can be utilized by the scientific community to conduct first-in-human studies. Poor presentation and interpretation of the data limit study reproducibility, and may result in rejection when the study is submitted to a journal, leading to loss of time and resources at multiple levels. In addition, inconsistencies in reporting the results of animal studies may limit the ability to extrapolate the experimental findings to humans. A few guidelines have been published to make the reporting of animal studie...
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 1, 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 - October 1, 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 - October 1, 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 - October 1, 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 - October 1, 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 - October 1, 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 - October 1, 2018 Category: Drugs & Pharmacology Source Type: research