Search results for "pharmacodynamics"
showing 10 items of 82 documents
Physiologically-Based Pharmacokinetic/Pharmacodynamic Model of MBQ-167 to Predict Tumor Growth Inhibition in Mice
2020
MBQ-167 is a dual inhibitor of the Rho GTPases Rac and Cdc42 that has shown promising results as an anti-cancer therapeutic at the preclinical stage. This drug has been tested in vitro and in vivo in metastatic breast cancer mouse models. The aim of this study is to develop a physiologically based pharmacokinetic/pharmacodynamic (PBPK-PD) model of MBQ-167 to predict tumor growth inhibition following intraperitoneal (IP) administration in mice bearing Triple Negative and HER2+ mammary tumors. PBPK and Simeoni tumor growth inhibition (TGI) models were developed using the Simcyp V19 Animal Simulator. Our developed PBPK framework adequately describes the time course of MBQ-167 in each of the mo…
Hemodilution in isolated tumor perfusion.
1984
Experiments are performed to study the influence of local hemodilution on tumor blood flow, oxygen availability in tumor tissue and O2 consumption of cancer cells. The results obtained clearly show that hemodilution in isolated tumor perfusion can distinctly improve nutritive blood flow through solid tumors. This can be utilized to enhance pharmacokinetics of antitumor drugs. Due to the improved metabolic status, the pharmacodynamics of some antitumor drugs should also be enhanced. To achieve a maximum improvement of the O2 supply to the tumor, hematocrit values should not be decreased below 0.20.
Status of Recombinant Factor VIII Concentrate Treatment for Hemophilia A in Italy: Characteristics and Clinical Benefits
2019
The current interest in recombinant factor VIII (rFVIII) products stems from the fact that they offer a technological solution to prolonging the half-life of and reducing the risk of formation of alloantibodies (inhibitors) against FVIII in treated patients with hemophilia A (HA). The Italian health care system has authorized the use of a wide range of rFVIII concentrates of the first, second, and third generation, as well as new innovative rFVIII preparates with an extended half-life (EHL) (Kogenate FS®-Bayer, belonging to the second generation and replaced since 2017 by a product consisting of the same modified molecule; because it is only available until the end of the current year, it w…
Liver and Statins: A Critical Appraisal of the Evidence.
2019
Adverse drug reactions (ADRs) represent an important cause of morbidity and mortality worldwide. Statins are a class of drugs whose main adverse effects are drug-induced liver injury (DILI) and myopathy. Some of these may be predictable, due to their pharmacokinetic and pharmacodynamic properties, while others, unfortunately, are idiosyncratic. Genetic factors may also influence patient susceptibility to DILI and myopathy in the case of statins. This review will first discuss the role of statins in cardiovascular disease treatment and prevention and the underlying mechanisms of action. Furthermore, to explore the susceptibility of statin-induced adverse events such as myopathy and hepatoto…
Retention pharmacokinetic and pharmacodynamic parameter relationships of antihistamine drugs using biopartitioning micellar chromatography
2001
Abstract Antihistamines are drugs which act by competitive inhibition of the H1 or H2 histamine receptors. Little has been known about their clinical pharmacokinetics and biological responses until the last few years. In this paper, we propose quantitative retention–activity relationship, QRAR, models based on the retention data of antihistamines in a biopartitioning micellar chromatography (BMC) system using a Brij35 mobile phase for describing pharmacokinetic parameters such as half-life and volume of distribution, or the pharmacodynamic parameters, therapeutic plasma levels, lethal doses and drug-receptor dissociation constant. The predictive ability of these models is statistically vali…
Pharmacokinetic/Pharmacodynamic Model of Neutropenia in Real-Life Palbociclib-Treated Patients
2021
Palbociclib is an oral CDK4/6 inhibitor indicated in HR+/HER2- advanced or metastatic breast cancer in combination with hormonotherapy. Its main toxicity is neutropenia. The aim of our study was to describe the kinetics of circulating neutrophils from real-life palbociclib-treated patients. A population pharmacokinetic (popPK) model was first constructed to describe palbociclib pharmacokinetic (PK). Individual PK parameters obtained were then used in the pharmacokinetic/pharmacodynamic (PK/PD) model to depict the relation between palbociclib concentrations and absolute neutrophil counts (ANC). The models were built with a population of 143 patients. Palbociclib samples were routinely collec…
Intubationsbedingungen nach Rocuronium und Succinylcholin
1996
OBJECTIVE Rocuronium is a new non-depolarising steroidal muscle relaxant with a short onset time. The present study was undertaken to compare intubating conditions as well as onset and clinical duration of a single dose of 0.6 mg/kg (2 x ED95) with a single dose of 1 mg/kg suxamethonium (3 x ED95). METHODS After obtaining informed consent and approval of the Ethics Committee, 40 adult patients (ASA I-III) participated in this study. After premedication with oxazepam, anaesthesia was induced with fentanyl and propofol and maintained with propofol, N2O and supplements of fentanyl as needed. Muscular relaxation was assessed by EMG recording of adductor pollicis muscle after supramaximal single…
A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refract…
2018
ABSTRACT We assessed the tolerability and antitumor activity of solitomab, a bispecific T-cell engager (BiTE®) antibody construct targeting epithelial cell adhesion molecule (EpCAM). Patients with relapsed/refractory solid tumors not amenable to standard therapy received solitomab as continuous IV infusion in a phase 1 dose-escalation study with six different dosing schedules. The primary endpoint was frequency and severity of adverse events (AEs). Secondary endpoints included pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. Sixty-five patients received solitomab at doses between 1 and 96 µg/day for ≥28 days. Fifteen patients had dose-limiting toxicities (DLTs): e…
Luspatercept Response in ESA-NaïVe/RS+ Patients and RS- Patients with Low-Intermediate Risk Myelodysplastic Syndromes (MDS)
2016
Abstract Background: Management of anemia is a common therapeutic challenge in patients with myelodysplastic syndromes (MDS). Luspatercept (ACE-536), a fusion protein containing modified activin receptor type IIB, is being developed for treatment of anemia in lower-risk MDS. Luspatercept binds GDF11 and other TGF-β superfamily ligands to promote late-stage erythroid differentiation and increase hemoglobin (Hgb) levels (Suragani R, Nat Med, 2014 and Attie K, Am J Hematol, 2014). Aims: This is an ongoing, phase 2, multicenter, open-label study to evaluate the effects of luspatercept in patient (pts) with low-intermediate risk MDS. Endpoints included erythroid response (IWG HI-E), RBC transfus…