Search results for "PHARMACOKINETICS"
showing 10 items of 458 documents
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…
Pharmacokinetics of acute and sub-chronic aripiprazole in P-glycoprotein deficient mice
2010
Abstract Background P-glycoprotein (P-gp), an efflux transporter localized in the blood–brain barrier, limits the access of multiple xenobiotics to the central nervous system (CNS). For the new antipsychotic aripiprazole and its active metabolite dehydroaripiprazole differences in disposition in blood and brain were investigated after acute and sub-chronic administration in a P-gp knockout mouse model. Methods Serum and brain concentrations of both drugs were measured at several time points 1–24 h after i.p. injection of 10 mg/kg aripiprazole and after 11 days of sub-chronic administration in several tissues. Moreover, the expression of P-gp was determined by Western blot analysis after sub…
Determination of the technetium-99m mercaptoacetyltriglycine plasma clearance in children by means of a single blood sample: a multicentre study
1993
A multicentre European study was undertaken in order to determine a reasonable algorithm allowing the determination of overall technetium-99m mercaptoacetyltriglycine clearance using a single blood sample. Employing multiple blood sample clearance as a reference method, it was shown that an acceptable estimation of the MAG3 renal clearance could be obtained using a blood sample taken at any time between 30 and 40 min after tracer injection. After correction for body surface area, comparison of clearance determined using (a) the single blood sample and (b) the multiple blood samples provided a coefficient of correlation of 0.949 and an SEE of 27 ml/min. This algorithm is valid for clearance …
Anthropometric measurements of the body composition of cancer patients determine the precise role of the body surface area and the calculation of the…
2012
The calculation of an accurate dose of chemotherapy for oncological patients reduces the possible medication errors and the toxicity of the body and so it improves the outcome of the treatment (survival). In oncological practice for the calculation of the dose of chemotherapy the human body surface area (BSA) is used. The human body surface area is determined by derived formulas, but it is not directly linked to the pharmacokinetics of the drugs. Pharmacokinetic studies have demonstrated that for the calculation of the chemotherapy dose the actual body weight should be taken into account rather than the ideal one. In the therapeutic dose determination the body fat mass has essential signifi…
Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Moxifloxacin Hydrochloride.
2020
Abstract In this monograph, literature data is reviewed to evaluate the feasibility of waiving in vivo bioequivalence testing and instead applying the Biopharmaceutics Classification System (BCS) based methods to the approval of immediate-release solid oral dosage forms containing moxifloxacin hydrochloride as the sole active pharmaceutical ingredient. To facilitate the feasibility decision, solubility and permeability and dissolution characteristics in the context of the BCS, therapeutic index, therapeutic use, pharmacokinetic parameters, bioequivalence/bioavailability issues, drug-excipient interactions and other relevant data were taken into consideration. Moxifloxacin is a BCS class I d…
Biotransformation in vitro of the 22R and 22S epimers of budesonide by human liver, bronchus, colonic mucosa and skin.
2001
The pharmacological effects of glucocorticoids are greatly influenced by their pharmacokinetic properties. In the present report, the in vitro biotransformation of the 22R and 22S epimers of the topical steroid budesonide was studied in the S-9 fraction of human liver, bronchus, skin and colonic mucosa. The disappearance of unchanged epimers of budesonide was measured during 90 min of incubation by high performance liquid chromatography. The rate of disappearance was high in human liver while little biotransformation occurred in bronchial tissue and colonic mucosa, and none was detected in the skin. A marked decay of the initial concentration of unchanged budesonide epimers was noticed afte…
24-h efficacy and pharmacokinetics of tiotropium Respimat® 5 μg in patients with asthma
2015
Background: Once-daily tiotropium Respimat® (tioR) add-on therapy has demonstrated efficacy in patients with moderate symptomatic asthma. Aim and Objectives: To investigate whether dosing regimen (QD vs BID) affected 24-h bronchodilator efficacy and exposure of tioR. Methods: 2 randomised, double-blind, crossover trials (trial 1, NCT01152450 [placebo-controlled]; trial 2, NCT01696071); 4-week treatments of tioR 5 µg QD, 2.5 µg BID and placebo Respimat® (pboR) added to medium-dose ICS (400-800 µg budesonide or equivalent). Primary end point (Week 4): area under the curve response for FEV1 (FEV1 AUC(0-24h)) (trial 1, tioR vs pboR; trial 2, QD vs BID). Pharmacokinetic end points (steady state)…