Search results for "Pharmacokinetic"
showing 10 items of 474 documents
Computer simulations for bioequivalence trials: Selection of analyte in BCS class II and IV drugs with first-pass metabolism, two metabolic pathways …
2018
A semi-physiological two compartment pharmacokinetic model with two active metabolites (primary (PM) and secondary metabolites (SM)) with saturable and non-saturable pre-systemic efflux transporter, intestinal and hepatic metabolism has been developed. The aim of this work is to explore in several scenarios which analyte (parent drug or any of the metabolites) is the most sensitive to changes in drug product performance (i.e. differences in in vivo dissolution) and to make recommendations based on the simulations outcome. A total of 128 scenarios (2 Biopharmaceutics Classification System (BCS) drug types, 2 levels of KM Pgp, in 4 metabolic scenarios at 2 dose levels in 4 quality levels of t…
An investigation of the stability of free and glucuronidated 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid in authentic urine samples.
2004
Preanalytical stability of a drug and its major metabolites is an important consideration in pharmacokinetic studies or whenever the analyte pattern is used to estimate drug habits. Firstly, the stability of free and glucuronidated 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH, THCCOOglu) in authentic urine samples was investigated. Random urine samples of cannabis users (n = 38) were stored at -20, 4, and 20 degrees C up to 15 days and up to 5 days at 40 degrees C, and alterations of the analyte pattern during storage were followed by liquid chromatography-tandem mass spectrometry. Secondly, the influence of pH (range 5.0-8.0) on the stability of the analytes was studied us…
Human Hepatic Cell Cultures: In Vitro and In Vivo Drug Metabolism
2003
Drug metabolism is the major determinant of drug clearance, and the factor most frequently responsible for inter-individual differences in drug pharmacokinetics. The expression of drug metabolising enzymes shows significant interspecies differences, and variability among human individuals (polymorphic or inducible enzymes) makes the accurate prediction of the metabolism of a new compound in humans difficult. Several key issues need to be addressed at the early stages of drug development to improve drug candidate selection: a) how fast the compound will be metabolised; b) what metabolites will be formed (metabolic profile); c) which enzymes are involved and to what extent; and d) whether dr…
Human pharmacokinetic (PK) characterization of the novel dual-action anti-HER3/EGFR antibody MEHD7945A (MEHD) in patients with refractory/recurrent e…
2012
2567 Background: MEHD is a novel dual-action human IgG1 antibody that blocks ligand binding to HER3 and EGFR, and elicits antibody-dependent cell-mediated cytotoxicity (ADCC). MEHD demonstrates single-agent activity in a broad panel of tumor models, including models resistant to anti-HER3 or anti-EGFR treatment alone. The objective of this analysis was to characterize the PK of MEHD associated with body weight (BW)-based dosing used in a phase I study in patients with epithelial tumors and to evaluate the potential for using fixed dosing in future studies. Methods: Preliminary non-compartmental and population PK analyses were performed using patient data from the dose-escalation stage [1, …
Folate-targeted supramolecular vesicular aggregates as a new frontier for effective anticancer treatment in in vivo model.
2012
Abstract Supramolecular vesicular aggregates (SVAs), made up by self-assembling liposomes and polyasparthydrazide co-polymers conjugated to folic acid molecules were extensively investigated in this manuscript as potential active targeting formulation for anticancer drug delivery. Folate-targeted systems (FT-SVAs) were used to treat breast cancer and to further proof the potential in vivo administration of these systems for the therapeutic treatment for several aggressive solid tumors. The physicochemical and technological parameters of FT-SVAs are suitable for their potential in vivo administration. The chemotherapeutic activity of GEM-loaded FT-SVAs was increased during in vivo experiment…
Tumor Blood Flow and O2 Availability during Hemodilution
1984
An insufficient and heterogeneously distributed nutritive blood flow leads to an inadequate and nonuniform supply of O2 and substrates in many solid tumors (Vaupel, 1977, 1979, 1982). This deterioration of the supply conditions, which already occurs in very early growth stages and which is superimposed by a deterioration of diffusive transport during advanced growth stages, is paralleled by a decrease in the therapeutic efficacy of various cancer treatment modalities such as irradiation and chemotherapy with antiproliferative drugs. In the case of anticancer drugs, the efficiency may be reduced by affecting both pharmacokinetics and pharmacodynamics. In the latter case this is due to the de…
Uptake mechanism of ApoE-modified nanoparticles on brain capillary endothelial cells as a blood-brain barrier model.
2012
Background The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood. Methodology/Principal Findings In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytome…
Safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of the novel enzyme replacement therapy avalglucosidase alfa (neoG…
2019
This multicenter/multinational, open-label, ascending-dose study (NCT01898364) evaluated safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of repeat-dose avalglucosidase alfa (neoGAA), a second-generation, recombinant acid α-glucosidase replacement therapy, in late-onset Pompe disease (LOPD). Patients ≥18 years, alglucosidase alfa naïve (Naïve) or previously receiving alglucosidase alfa for ≥9 months (Switch), with baseline FVC ≥50% predicted and independently ambulatory, received every-other-week avalglucosidase alfa 5, 10, or 20 mg/kg over 24 weeks. 9/10 Naïve and 12/14 Switch patients completed the study. Avalglucosidase alfa was well-tolerated; no deaths…
Choosing the Right Antifungal Agent in ICU Patients
2019
Fungi are responsible for around 20% of microbiologically documented infections in intensive care units (ICU). In the last decade, the incidence of invasive fungal infections (IFI), including candidemia, has increased steadily because of increased numbers of both immunocompromised and ICU patients. To improve the outcomes of patients with IFI, intensivists need to be aware of the inherent challenges. This narrative review summarizes the features of routinely used treatments directed against IFI in non-neutropenic ICU patients, which include three classes of antifungals: polyenes, azoles, and echinocandins. ICU patients' pathophysiological changes are responsible for deep changes in the phar…
PET: Theoretical Background and Practical Aspects
2012
Positron emission tomography (PET) is a nuclear medicine imaging tool utilized for investigation of physiological processes in vivo. PET uses the decay characteristics of positron-emitting radionuclides which are produced in a cyclotron and then used to label compounds involved in physiological processes. Usually, the labeled compound—the tracer—is administered intravenously and distributed in the tissue. The radionuclide decays and the emitted photons are detected by the PET scanner. PET then offers the possibility to compute three-dimensional images of the biodistribution and kinetics of the regional radioactivity concentration. There are several options to analyze reconstructed PET image…