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https://www.readbyqxmd.com/read/27914040/formulation-optimization-and-ex-vivo-and-in-vivo-evaluation-of-celecoxib-microemulsion-based-gel-for-transdermal-delivery
#1
Mengyuan Cao, Lili Ren, Guoguang Chen
Celecoxib (CXB) is a poorly aqueous solubility sulfonamide non-steroidal anti-inflammatory drug (NSAID). Hence, the formulation of CXB was selected for solubilization and bioavailability. To find out suitable formulation for microemulsion, the solubility of CXB in triacetin (oil phase), Tween 80 (surfactant), and Transcutol-P (co-surfactant) was screened respectively and optimized by using orthogonal experimental design. The Km value and concentration of oil, Smix, and water were confirmed by pseudo-ternary phase diagram studies and central composite design...
December 2, 2016: AAPS PharmSciTech
https://www.readbyqxmd.com/read/27913881/phase-ii-trial-of-s-1-plus-leucovorin-in-patients-with-advanced-gastric-cancer-and-clinical-prediction-by-s-1-pharmacogenetic-pathway
#2
Ming-Ming He, Dong-Sheng Zhang, Feng Wang, Zi-Xian Wang, Shu-Qiang Yuan, Zhi-Qiang Wang, Hui-Yan Luo, Chao Ren, Miao-Zhen Qiu, Ying Jin, De-Shen Wang, Dong-Liang Chen, Zhao-Lei Zeng, Yu-Hong Li, Yang-Yang He, Yuan-Tao Hao, Pi Guo, Feng-Hua Wang, Yi-Xin Zeng, Rui-Hua Xu
BACKGROUND: The first one-arm phase II trial aimed to evaluate and predict efficacy and safety of S-1 plus oral leucovorin (S-1/LV) as first-line chemotherapy for patients with advanced gastric cancer (AGC), using S-1 pharmacogenetic pathway approach. PATIENTS AND METHODS: A total of 39 patients orally took S-1 at conventional dose and LV simultaneously at a dose of 25 mg twice daily for a week, within a 2-week cycle. The primary endpoint was overall response rate (ORR), while the secondary endpoints were progression-free survival (PFS), time to failure (TTF), overall survival (OS), disease control rate (DCR), and adverse events (AEs)...
December 2, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27913821/theobromine-upregulates-osteogenesis-by-human-mesenchymal-stem-cells-in-vitro-and-accelerates-bone-development-in-rats
#3
Bret H Clough, Joni Ylostalo, Elizabeth Browder, Eoin P McNeill, Thomas J Bartosh, H Ralph Rawls, Tetsuo Nakamoto, Carl A Gregory
Theobromine (THB) is one of the major xanthine-like alkaloids found in cacao plant and a variety of other foodstuffs such as tea leaves, guarana and cola nuts. Historically, THB and its derivatives have been utilized to treat cardiac and circulatory disorders, drug-induced nephrotoxicity, proteinuria and as an immune-modulator. Our previous work demonstrated that THB has the capacity to improve the formation of hydroxyl-apatite during tooth development, suggesting that it may also enhance skeletal development...
December 2, 2016: Calcified Tissue International
https://www.readbyqxmd.com/read/27913584/nitro-fatty-acid-pharmacokinetics-in-the-adipose-tissue-compartment
#4
Marco Fazzari, Nicholas K H Khoo, Steven R Woodcock, Diane K Jorkasky, Lihua Li, Francisco J Schopfer, Bruce A Freeman
Electrophilic nitro-fatty acids (NO2-FAs) promote adaptive and anti-inflammatory cell signaling responses as a result of an electrophilic character that supports post-translational protein modifications. A unique pharmacokinetic profile is expected for NO2-FAs because of an ability to undergo reversible reactions including Michael additions with biological cysteine-containing proteins and esterification into complex lipids. Herein we report via quantitative whole-body autoradiography analysis of rats gavaged with radiolabeled 10-nitro-[14C]oleic acid, preferential accumulation in adipose tissue over two weeks...
December 2, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27913542/new-therapies-for-hemophilia
#5
Steven W Pipe
Individuals with severe hemophilia have benefitted from 5 decades of advances that have led to widespread availability of safe and efficacious factors VIII and IX, a multidisciplinary integrated care model through a network of specialized hemophilia treatment centers, and aggressive introduction of prophylactic replacement therapy to prevent bleeding and preserve joint health. Yet, there are remaining challenges and treatment gaps which have prevented complete abrogation of all joint bleeding, and progressive joint deterioration may continue in some affected individuals over the course of a lifetime...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913535/reversing-vitamin-k-antagonists-making-the-old-new-again
#6
Sabine Eichinger
Vitamin K antagonists (VKAs) are commonly used for the prevention and treatment of thrombotic disorders. The response to VKAs is highly variable due to their specific interaction with the vitamin K cycle, and hence interference with hepatic synthesis of vitamin K-dependent coagulation factors. Monitoring the anticoagulant effect of VKAs by assessing the patient's international normalized ratio (INR) is essential because complications are closely related to the intensity of anticoagulation. Treatment with VKAs contains a substantial risk of bleeding with a high case fatality rate...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913478/thrombosis-in-the-setting-of-obesity-or-inflammatory-bowel-disease
#7
Steven R Lentz
Obesity and inflammatory bowel disease (IBD) are systemic inflammatory disorders that predispose to arterial and venous thrombosis through similar prothrombotic mechanisms. Obesity and IBD are chronic risk factors that lead to a persistently elevated risk of thrombosis, although the thrombotic risk with IBD appears to wax and wane with disease severity. Because of the lack of high-quality evidence to guide management decisions, approaches to the prevention and treatment of thrombosis in patients with obesity or IBD are based on extrapolation from general guidelines for antithrombotic therapy...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913319/assessing-the-benefits-of-targeted-drug-delivery-by-nanocarriers-a-partico-pharmacokinetic-framework
#8
Ronald A Siegel, Ameya R Kirtane, Jayanth Panyam
OBJECTIVE: An in vivo kinetic framework is introduced to analyze and predict the quantitative advantage of using nanocarriers to deliver drugs, especially anticancer agents, compared to administering the same drugs in their free form. METHODS: This framework recognizes three levels of kinetics. First is the particokinetics associated with deposition of nanocarriers into tissues associated with drug effect and toxicity, their residence inside those tissues, and elimination of the nanocarriers from the body...
November 29, 2016: IEEE Transactions on Bio-medical Engineering
https://www.readbyqxmd.com/read/27913162/intranasal-delivery-of-antipsychotic-drugs
#9
REVIEW
Yogesh K Katare, Justin E Piazza, Jayant Bhandari, Ritesh P Daya, Kosalan Akilan, Madeline J Simpson, Todd Hoare, Ram K Mishra
Antipsychotic drugs are used to treat psychotic disorders that afflict millions globally and cause tremendous emotional, economic and healthcare burdens. However, the potential of intranasal delivery to improve brain-specific targeting remains unrealized. In this article, we review the mechanisms and methods used for brain targeting via the intranasal (IN) route as well as the potential advantages of improving this type of delivery. We extensively review experimental studies relevant to intranasal delivery of therapeutic agents for the treatment of psychosis and mental illnesses...
November 29, 2016: Schizophrenia Research
https://www.readbyqxmd.com/read/27912846/new-insights-and-evolving-role-of-pegylated-liposomal-doxorubicin-in-cancer-therapy
#10
REVIEW
Alberto A Gabizon, Yogita Patil, Ninh M La-Beck
We herein review various pharmacological and clinical aspects of pegylated liposomal doxorubicin (PLD), the first nanomedicine to be approved for cancer therapy, and discuss the gap between its potent antitumor activity in preclinical studies and its comparatively modest achievements in clinical studies and limited use in clinical practice. PLD is a complex formulation of doxorubicin based on pharmaceutical nanotechnology with unique pharmacokinetic and pharmacodynamic properties. Its long circulation time with stable retention of the payload and its accumulation in tumors with high vascular permeability both result in important advantages over conventional chemotherapy...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27911829/supramolecular-pegylation-of-biopharmaceuticals
#11
Matthew J Webber, Eric A Appel, Brittany Vinciguerra, Abel B Cortinas, Lavanya S Thapa, Siddharth Jhunjhunwala, Lyle Isaacs, Robert Langer, Daniel G Anderson
The covalent modification of therapeutic biomolecules has been broadly explored, leading to a number of clinically approved modified protein drugs. These modifications are typically intended to address challenges arising in biopharmaceutical practice by promoting improved stability and shelf life of therapeutic proteins in formulation, or modifying pharmacokinetics in the body. Toward these objectives, covalent modification with poly(ethylene glycol) (PEG) has been a common direction. Here, a platform approach to biopharmaceutical modification is described that relies on noncovalent, supramolecular host-guest interactions to endow proteins with prosthetic functionality...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911381/a-novel-approach-for-the-administration-of-medications-and-fluids-in-emergency-scenarios-and-settings
#12
Akilesh Honasoge, Neal Lyons, Kathleen Hesse, Braden Parker, Robert Mokszycki, Kelly Wesselhoff, Rolla Sweis, Erik B Kulstad
The available routes of administration commonly used for medications and fluids in the acute care setting are generally limited to oral, intravenous, or intraosseous routes, but in many patients, particularly in the emergency or critical care settings, these routes are often unavailable or time-consuming to access. A novel device is now available that offers an easy route for administration of medications or fluids via rectal mucosal absorption (also referred to as proctoclysis in the case of fluid administration and subsequent absorption)...
November 9, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911120/new-frontiers-in-anticoagulation-non-vitamin-k-oral-anticoagulants-in-stroke-prevention
#13
Valentina Arnao, Marianna Riolo, Antonino Tuttolomondo, Antonio Pinto, Brigida Fierro, Paolo Aridon
Non vitamin-K oral anticoagulants (NOACs) are direct and specific inhibitors of the coagulation factors IIa (dabigatran) and Xa (apixaban, rivaroxaban, edoxaban) which share many pharmacokinetic properties. However, indications are lacking regarding the use of NOACs during thrombolysis, surgery and bleeding events. Areas covered: In this paper, the authors retrospectively analyzed the relevant literature on the NOACs using the PubMed and Google Scholar databases. Expert Commentary: Although warfarin is effective in cardioembolic stroke prevention, easier handling and more favorable risk-benefit profile often render NOACs a more preferable therapy choice for neurologists...
December 2, 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27911112/treatment-of-alpha-and-beta-herpesvirus-infections-in-solid-organ-transplant-recipients
#14
C L Abad, R R Razonable
Human herpesviruses frequently cause infections in solid organ transplant (SOT) recipients. Areas covered: We provide an overview of the clinical impact of alpha and beta herpesviruses and highlight the mechanisms of action, pharmacokinetics, clinical indications, and adverse effects of antiviral drugs for the management of herpes simplex virus, varicella zoster virus and cytomegalovirus. We comprehensively evaluated key clinical trials that led to drug approval, and served as the foundation for management guidelines...
December 2, 2016: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/27910963/daratumumab-monoclonal-antibody-therapy-to-treat-multiple-myeloma
#15
C Xia, M Ribeiro, S Scott, S Lonial
Daratumumab (Darzalex[TM]) is a human monoclonal antibody (MAb) that targets CD38; a surface protein highly expressed across multiple myeloma (MM) cells. Preclinical studies have shown daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), apoptosis upon secondary crosslinking and immunomodulatory effects via a decrease in immune suppressive cells. Daratumumab has a favorable toxicity profile and encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide) and stem cell transplant have already failed...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27910780/naringenin-ameliorates-doxorubicin-toxicity-and-hypoxic-condition-in-dalton-s-lymphoma-ascites-tumor-mouse-model-evidence-from-electron-paramagnetic-resonance-imaging
#16
Venkatesan Kathiresan, Swathika Subburaman, Arun Venkatesh Krishna, Mathivanan Natarajan, Gandhidasan Rathinasamy, Kumaresan Ganesan, Murugesan Ramachandran
Doxorubicin (DOX) is a well-known cytotoxic agent used extensively as a chemotherapeutic drug to eradicate a wide variety of human cancers. Reactive oxygen species (ROS)-mediated oxidative stress during DOX treatment can induce cardiac, renal, and hepatic toxicities, which can constrain its use as a potential cytotoxic agent. The present work investigates the antioxidant potential of naringenin (NAR) against DOXinduced toxicities of a Dalton's lymphoma ascites (DLA) tumor-bearing mouse model. Mice were randomized into four groups: a negative control, positive control, DOX (2...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27910765/gene-therapy-for-rheumatoid-arthritis
#17
Shuang Liu, Kazutaka Maeyama
With the aim of controlling disease relapse and bone deformation of individual joints, the application of gene therapy in rheumatoid arthritis (RA) has slowly progressed on a trial-and-error basis. Several new therapeutic targets have been identified in preclinical studies in animal models, although a limited number of gene-based clinical trials have been conducted. In this article, we summarize the status of gene therapy for RA by addressing issues related to innovating drug development. More disease- and target-specific preclinical tests are required to overcome the insufficient information regarding pharmacokinetics and toxicokinetics, which are related to safety issues in the field of RA gene therapy...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27910712/development-of-a-nanogel-formulation-for-transdermal-delivery-of-tenoxicam-a-pharmacokinetic-pharmacodynamic-modeling-approach-for-quantitative-prediction-of-skin-absorption
#18
Mohammed H Elkomy, Shahira F El Menshawe, Hussein M Eid, Ahmed M A Ali
This study investigates potentials of solid lipid nanoparticles (SLN) based gel for transdermal delivery of tenoxicam (TNX) and describes a pharmacokinetics-pharmacodynamics (PK-PD) modeling approach for predicting concentration-time profile in skin. A 2(3) factorial design was adopted to study the effect of formulation factors on SLN properties and determine the optimal formulation. SLN-gel tolerability was investigated using rabbit skin irritation test. Its anti-inflammatory activity was assessed by carrageenan induced rat paw edema test...
December 2, 2016: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/27910037/effect-of-activated-charcoal-on-rivaroxaban-complex-absorption
#19
Edouard Ollier, Sophie Hodin, Julien Lanoiselée, Jean Escal, Sandrine Accassat, Elodie De Magalhaes, Thierry Basset, Laurent Bertoletti, Patrick Mismetti, Xavier Delavenne
OBJECTIVE: To quantify the impact of activated charcoal (AC) on rivaroxaban exposure in healthy volunteers. METHODS: This was an open-label study with an incomplete cross-over design of single-dose rivaroxaban (40 mg) administered alone or with AC in 12 healthy volunteers. The study comprised three treatment periods in randomised sequence, one with rivaroxaban administered alone and two with AC given at 2, 5 or 8 h post-dose. Rivaroxaban plasma concentration was measured in blood samples drawn at 16 time points...
December 2, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27910036/evaluation-of-the-pharmacokinetic-interaction-between-venetoclax-a-selective-bcl-2-inhibitor-and-warfarin-in-healthy-volunteers
#20
Ahmed Hamed Salem, Beibei Hu, Kevin J Freise, Suresh K Agarwal, Dilraj S Sidhu, Shekman L Wong
BACKGROUND AND OBJECTIVE: Venetoclax is a selective, B-cell lymphoma-2 inhibitor that has demonstrated clinical efficacy in a variety of hematological malignancies. In vitro data indicated weak cytochrome P450 (CYP) 2C9 inhibition by venetoclax; however, it is not predicted to cause clinically relevant inhibition due to high plasma protein binding. A Phase 1 study was conducted in healthy volunteers to evaluate the effect of venetoclax on warfarin pharmacokinetics. METHODS: Subjects received a single oral dose of 5 mg warfarin on day 1 of both periods 1 and 2, separated by a 14 days washout...
December 2, 2016: Clinical Drug Investigation
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