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

Longitudinal Pharmacokinetics of Mycophenolic Acid in Elderly Renal Transplant Recipients Compared to a Younger Control Group: Data from the nEverOld Trial
ConclusionsThese data show that the pharmacokinetics of MPA in elderly renal transplant recipients were no different to those of younger-adult recipients in this study population.Clinicaltrials.govNCT 01631058. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - September 18, 2018 Category: Drugs & Pharmacology Source Type: research

Determination of the Pharmacokinetics and Tissue Distribution of Methyl 3,4-Dihydroxybenzoate (MDHB) in Mice Using Liquid Chromatography-Tandem Mass Spectrometry
ConclusionsThe pharmacokinetic characteristics of MDHB include fast absorption, high systemic clearance, a short half-life and an oral bioavailability of 23%. Additionally, MDHB permeates the blood-brain barrier (BBB) and is rapidly distributed to all organs. The identification of the pharmacokinetics of MDHB following its oral administration will contribute to further preclinical and clinical studies of its effects. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - September 17, 2018 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics and Bioavailability Enhancement of Baicalin: A Review
AbstractBaicalin is one of the major bioactive components ofScutellaria radix, a Chinese herb that has been used since ancient times. Baicalin has various pharmacological activities, including antitumor, antimicrobial, and antioxidant, and has wide clinical applications. Baicalin displays a distinct pharmacokinetic profile including gastrointestinal hydrolysis, enterohepatic recycling, carrier-mediated transport, and complicated metabolism. The in vivo disposition of baicalin is affected by combinations of other herbs and baicalin can interact with other co-administered drugs due to competition between metabolic enzymes an...
Source: European Journal of Drug Metabolism and Pharmacokinetics - September 12, 2018 Category: Drugs & Pharmacology Source Type: research

Intestinal Absorption of Isoalantolactone and Alantolactone, Two Sesquiterpene Lactones from Radix Inulae, Using Caco-2 Cells
ConclusionOur results demonstrated that the absorption permeability of isoalantolactone and alantolactone was good in the Caco-2 cell model. The isoalantolactone and alantolactone absorption elucidated in this study provides useful information for further pharmacokinetics studies. Since low intestinal absorption can now be ruled out as a cause, further studies are needed to explain the low oral bioavailability of the two sesquiterpene lactones. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - September 12, 2018 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics and Bioavailability Enhancement of Baicalin: A Review
AbstractBaicalin is one of the major bioactive components ofScutellaria radix, a Chinese herb that has been used since ancient times. Baicalin has various pharmacological activities, including antitumor, antimicrobial, and antioxidant, and has wide clinical applications. Baicalin displays a distinct pharmacokinetic profile including gastrointestinal hydrolysis, enterohepatic recycling, carrier-mediated transport, and complicated metabolism. The in vivo disposition of baicalin is affected by combinations of other herbs and baicalin can interact with other co-administered drugs due to competition between metabolic enzymes an...
Source: European Journal of Drug Metabolism and Pharmacokinetics - September 12, 2018 Category: Drugs & Pharmacology Source Type: research

Intestinal Absorption of Isoalantolactone and Alantolactone, Two Sesquiterpene Lactones from Radix Inulae, Using Caco-2 Cells
ConclusionOur results demonstrated that the absorption permeability of isoalantolactone and alantolactone was good in the Caco-2 cell model. The isoalantolactone and alantolactone absorption elucidated in this study provides useful information for further pharmacokinetics studies. Since low intestinal absorption can now be ruled out as a cause, further studies are needed to explain the low oral bioavailability of the two sesquiterpene lactones. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - September 12, 2018 Category: Drugs & Pharmacology Source Type: research

Correction to: Evaluation of Generic Methods to Predict Human Pharmacokinetics Using Physiologically Based Pharmacokinetic Model for Early Drug Discovery of Tyrosine Kinase Inhibitors
The original version of this article unfortunately contained a mistake. Conflict of interest statement was incorrect. The corrected COI statement is given below. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - September 11, 2018 Category: Drugs & Pharmacology Source Type: research

The Influence of Diabetes Mellitus on Glucuronidation and Sulphation of Paracetamol in Patients with Febrile Neutropenia
ConclusionsNo differences in the pharmacokinetics of APAP, APAP-glu and APAP-sulfate in patients with FN indicates that diabetes does not influence glucuronidation and sulfatation of paracetamol. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - September 5, 2018 Category: Drugs & Pharmacology Source Type: research

Impact of Efavirenz Metabolism on Loss to Care in Older HIV+ Africans
ConclusionOlder age was associated with loss to care, especially among those with slow efavirenz metabolism. Understanding the relationship between older age and CYP2B6 genotype will be important to improving outcomes in an aging population initiating efavirenz-based ART in similar settings. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - August 30, 2018 Category: Drugs & Pharmacology Source Type: research

Evaluation of Drug Biliary Excretion Using Sandwich-Cultured Human Hepatocytes
AbstractEvaluation of hepatobiliary transport of drugs is an important challenge, notably during the development of new molecular identities. In this context, sandwich-cultured human hepatocytes (SCHH) have been proposed as an interesting and integrated tool for predicting in vitro biliary excretion of drugs. The present review was therefore designed to summarize key findings about SCHH, including their establishment, their main functional features and their use for the determination of canalicular transport and the prediction of in vivo biliary clearance and hepatobiliary excretion-related drug –drug interactions. R...
Source: European Journal of Drug Metabolism and Pharmacokinetics - August 30, 2018 Category: Drugs & Pharmacology Source Type: research

Impact of Efavirenz Metabolism on Loss to Care in Older HIV+ Africans
ConclusionOlder age was associated with loss to care, especially among those with slow efavirenz metabolism. Understanding the relationship between older age and CYP2B6 genotype will be important to improving outcomes in an aging population initiating efavirenz-based ART in similar settings. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - August 30, 2018 Category: Drugs & Pharmacology Source Type: research

Clinical Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants in Patients with Renal Failure
AbstractA recent survey on the use of direct oral anticoagulants (DOACs) revealed that 43% of patients with atrial fibrillation and renal impairment were potentially overdosed and had a hazard ratio for major bleeding of 2.19. In this review, we analyse and discuss the effect of renal failure on the pharmacokinetics and pharmacodynamics of DOACs and of strategies proposed to adjust doses according to the level of renal dysfunction. The pharmacokinetic characteristics of available DOACs (dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban) differ substantially as regards oral bioavailability, plasma protein binding and ...
Source: European Journal of Drug Metabolism and Pharmacokinetics - August 30, 2018 Category: Drugs & Pharmacology Source Type: research

Evaluation of Drug Biliary Excretion Using Sandwich-Cultured Human Hepatocytes
AbstractEvaluation of hepatobiliary transport of drugs is an important challenge, notably during the development of new molecular identities. In this context, sandwich-cultured human hepatocytes (SCHH) have been proposed as an interesting and integrated tool for predicting in vitro biliary excretion of drugs. The present review was therefore designed to summarize key findings about SCHH, including their establishment, their main functional features and their use for the determination of canalicular transport and the prediction of in vivo biliary clearance and hepatobiliary excretion-related drug –drug interactions. R...
Source: European Journal of Drug Metabolism and Pharmacokinetics - August 30, 2018 Category: Drugs & Pharmacology Source Type: research

Effect of CYP2C9 Polymorphisms on the Pharmacokinetics of Indomethacin During Pregnancy
ConclusionAlthough our results are limited by sample size and are not statistically significant, these data suggest that certain genetic polymorphisms ofCYP2C9 may lead to an increased metabolic ratio and an increase in the clearance of indomethacin. More data are needed to assess the impact ofCYP2C9 genotype on the effectiveness of indomethacin as a tocolytic agent. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - August 29, 2018 Category: Drugs & Pharmacology Source Type: research

Simultaneous Determination of Rivaroxaban and Enalapril in Rat Plasma by UPLC –MS/MS and Its Application to A Pharmacokinetic Interaction Study
AbstractBackground and ObjectivesThere have been no animal experiments and clinical studies on the pharmacokinetic interaction between rivaroxaban and enalapril. To investigate whether a potential pharmacokinetic interaction is present between rivaroxaban and enalapril, a rapid and sensitive Ultra performance liquid chromatography —tandem mass spectrometry (UPLC–MS/MS) method was developed and validated to determine the concentration of rivaroxaban and enalapril in rat plasma and was then applied to a pharmacokinetic interaction study.MethodsThe analytes were separated on an Acquity UPLC BEH C18 chromatography ...
Source: European Journal of Drug Metabolism and Pharmacokinetics - August 27, 2018 Category: Drugs & Pharmacology Source Type: research

Predicting Human Pharmacokinetics: Physiologically Based Pharmacokinetic Modeling and In Silico ADME Prediction in Early Drug Discovery
(Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - August 23, 2018 Category: Drugs & Pharmacology Source Type: research

Biodistribution and Pharmacokinetics of Amblyomin-X, a Novel Antitumour Protein Drug in Healthy Mice
ConclusionsThese findings suggest that amblyomin-X is rapidly distributed to the tissues, metabolized by the liver or even kidneys, and eliminated in urine in healthy mice. There is no accumulation in any organ. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - August 21, 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 - August 16, 2018 Category: Drugs & Pharmacology Source Type: research

Influence of Orally Administered Borneol on the Expression of Hepatic Transporters in Rats
ConclusionsOral administration of borneol may affect the metabolism of substances that are involved in bile acid enterohepatic circulation and substrates of Ntcp, Mdrla, Mrp2 and Mrp4 transporters. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - August 13, 2018 Category: Drugs & Pharmacology Source Type: research

Clinical Pharmacokinetics and Drug Interactions of Doravirine
AbstractDoravirine is a new HIV-1 non-nucleoside reverse transcriptase inhibitor that has demonstrated a good efficacy and safety profile in clinical trials. It has a therapeutic profile that makes it an attractive option for treatment of HIV-1 infection. As such, there has been an increase in the published literature regarding the pharmacokinetics of doravirine and potential for drug –drug interactions. This review aimed to identify pharmacokinetic literature pertaining to doravirine, used findings from the literature to summarize its pharmacokinetic profile, and finally evaluated literature describing actual and po...
Source: European Journal of Drug Metabolism and Pharmacokinetics - July 25, 2018 Category: Drugs & Pharmacology Source Type: research

Evaluation of Generic Methods to Predict Human Pharmacokinetics Using Physiologically Based Pharmacokinetic  Model for Early Drug Discovery of Tyrosine Kinase Inhibitors
AbstractBackgroundRequirements for predicting human pharmacokinetics in drug discovery are increasing. Developing different methods of human pharmacokinetic prediction will facilitate lead optimization, candidate nomination, and dosing regimens before clinical trials at various early drug discovery stages.ObjectivesTo develop and validate generic methods of human pharmacokinetic prediction to meet the requirements in early drug discovery.MethodsThe physiologically based pharmacokinetic (PBPK) model implemented in Gastroplus ™ was used for human pharmacokinetic predictions. The absorption, distribution, metabolism, an...
Source: European Journal of Drug Metabolism and Pharmacokinetics - July 23, 2018 Category: Drugs & Pharmacology Source Type: research

Reduced Clearance of Phenobarbital in Advanced Cancer Patients near the End of Life
AbstractBackground and ObjectivesLittle is known about the pharmacokinetics of phenobarbital in terminally ill cancer patients. We investigated whether phenobarbital clearance alters depending on the length of survival.MethodsWe retrospectively reviewed the clinical, laboratory, and therapeutic drug monitoring (TDM) records of patients who received parenteral or oral phenobarbital for 21 consecutive days or longer between 2000 and 2016. Patients were divided into non-cancer and cancer groups. Cancer patients were further stratified according to the survival interval after TDM: those who survived  >  3 ...
Source: European Journal of Drug Metabolism and Pharmacokinetics - July 19, 2018 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics of Tramadol and Celecoxib in Japanese and Caucasian Subjects Following Administration of Co-Crystal of Tramadol-Celecoxib (CTC): A Randomised, Open-Label Study
ConclusionsDifferences in pharmacokinetics were not sufficient to suggest that CTC dose adjustment is required in Japanese subjects.Clinical Trial RegistrationEudraCT: 2015-003071-29. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 28, 2018 Category: Drugs & Pharmacology Source Type: research

Model-Informed Approaches for Alternative Aripiprazole Dosing Regimens and Missed Dose Management: Towards Better Adherence to Antipsychotic Pharmacotherapy
(Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 26, 2018 Category: Drugs & Pharmacology Source Type: research

Application of a Volumetric Absorptive Microsampling Device to a Pharmacokinetic Study of Tacrolimus in Rats: Comparison with Wet Blood and Plasma
ConclusionsCollectively, these findings suggest that the VAMS device can be a useful device for pharmacokinetic studies in rats. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 25, 2018 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetic Modeling of Remifentanil in Infants with Unrepaired Tetralogy of Fallot
ConclusionsUnrepaired TOF does not change the pharmacokinetics of remifentanil, suggesting a similar dosage for infants with TOF compared to normal cardiac anatomy infants.Clinical Trial RegistrationThe patient enrollment in this study started at 2012, so we do not have clinic trial number, but we still think this is a valuable research and hope it could be considered for publication. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 19, 2018 Category: Drugs & Pharmacology Source Type: research

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