Search results for "pharmacokinetic"
showing 10 items of 474 documents
Evaluation of atezolizumab immunogenicity: Efficacy and safety (Part 2).
2022
Abstract Antibody therapeutics can be associated with unwanted immune responses resulting in the development of anti‐drug antibodies (ADA). Optimal methods to evaluate the potential effects of ADA on clinical outcomes in oncology are not well established. In this study, we assessed efficacy and safety, based on ADA status, in patients from over 10 clinical trials that evaluated the immune checkpoint inhibitor atezolizumab as a single agent or as combination therapy for several types of advanced cancers. ADA can only be observed post randomization, and imbalances in baseline prognostic factors can confound the interpretation of ADA impact. We applied methodology to account for the confoundin…
Population pharmacokinetics of 5-fluorouracil in colorectal cancer patients
2004
Aims. The pharmacokinetics of 5-fluorouracil (5-FU) after intravenous administration in color- ectal cancer patients were examined using population analysis. The relevant covariates and the extent of inter- and intraindividual variability were evaluated. Methods. Data from 27 patients with diagnosis of nonmetastatic colorectal adenocarcinoma receiving weekly 5-FU (450 mg/m2), plus levamisol 50 mg/8 hours by oral route for 3 days every 15 days, were pooled with data from 17 patients with diagnosis of metastatic colorectal adenocarcinoma, receiving daily 5-FU (425 mg/m2) and intravenous folinic acid (20 mg/m2) over five consecutive days (daily times five), every four weeks. In both groups 5-…
Systemic chemotherapy and pressurized intraperitoneal aerosol chemotherapy (PIPAC): A case report of a multimodal treatment for peritoneal metastases…
2020
Highlights • Integration of PIPAC to systemic chemotherapy can have good tolerance profile. • Repeated biopsies performed during PIPAC allowed therapy-response monitoring. • Analysis of biopsies performed during PIPAC allowed tailoring of chemotherapy. • Integration of PIPAC to systemic chemotherapy can permit good quality of life.
Population Pharmacokinetics of Palbociclib in aReal-World Situation
2021
Palbociclib is an oral cyclin-dependent kinase inhibitor that is used in combination with aromatase inhibitors in the treatment of postmenopausal women with metastatic breast cancer. Its metabolism profile is associated with an important interpatient variability. We performed a population pharmacokinetics study of palbociclib in women routinely followed in a cancer center. One hundred and fifty-one samples were analyzed. The sampling times after administration ranged from 0.9 to 75 h and the samples were taken between 1 and 21 days after the beginning of the palbociclib cycle. Palbociclib was determined using a validated mass spectrometry method. The best model that described the concentrat…
A promising camptothecin derivative: Semisynthesis, antitumor activity and intestinal permeability.
2014
Oral administration of camptothecin (Cm) derivatives and other antitumoral agents is being actively developed in order to improve the quality of life of patients with cancer. Though several lipophilic derivatives of CPT have shown interesting oral bioavailability in preclinical and clinical studies, only Topotecan has been approved for this route of administration. Semisynthesis, antitumor activity, biological inhibition mechanism, and in situ intestinal permeability of 9, 10-[1,3]-Dioxinocamptothecin (CDiox), an unexplored CPT derivative, have been studied in this paper. The hexacyclic analog was as effective as Topotecan and CPT in different tumor cell lines, showing an expected similar a…
2019
The widespread use of 68Ga for positron emission tomography (PET) relies on the development of radiopharmaceutical precursors that can be radiolabelled and dispensed in a simple, quick, and convenient manner. The DATA (6-amino-1,4-diazapine-triacetate) scaffold represents a novel hybrid chelator architecture possessing both cyclic and acyclic character that may allow for facile access to 68Ga-labelled tracers in the clinic. We report the first bifunctional DATA chelator conjugated to [Tyr3]octreotide (TOC), a somatostatin subtype 2 receptor (SST2)-targeting vector for imaging and functional characterisation of SSTR2 expressing tumours. The radiopharmaceutical precursor, DATA-TOC, was synthe…
Refining in vitro neurotoxicity testing--the development of blood-brain barrier models.
2003
The purpose of this paper is to review the current state of development of advanced in vitro blood–brain barrier (BBB) models. The BBB is a special capillary bed that separates the blood from the central nervous system (CNS) parenchyma. Astrocytes maintain the integrity of the BBB, and, without astrocytic contacts, isolated brain capillary endothelial cells in culture lose their barrier characteristics. Therefore, when developing in vitro BBB models, it is important to add astrocytic factors into the culture system. Recently, novel filter techniques and co-culture methods have made it possible to develop models which resemble the in vivo functions of the BBB in an effective way. With a BBB…
Evaluation of Galantamine transbuccal absorption by reconstituted human oral epithelium and porcine tissue as buccal mucosa models: Part I
2008
Over the last decade, interest in delivering drugs through buccal mucosa has increased. As a major limitation in buccal drug delivery could be the low permeability of the epithelium, the aim of this study was to evaluate the aptitude of galantamine, useful in Alzheimer's disease, to penetrate the buccal mucosa. The evaluation of the ability of galantamine to permeate through the buccal epithelium was investigated using two permeation models. Firstly, in vitro permeation experiments were carried out using reconstituted human oral non-keratinised epithelium and Transwell diffusion cells system. Results were validated by ex vivo experiments using porcine buccal mucosa as membrane and Franz typ…
Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Folic Acid.
2018
This work presents a review of literature and experimental data relevant to the possibility of waiving pharmacokinetic bioequivalence studies in human volunteers for approval of immediate-release solid oral pharmaceutical forms containing folic acid as the single active pharmaceutical ingredient. For dosage forms containing 5 mg folic acid, the highest dose strength on the World Health Organization Essential Medicines List, the dose/solubility ratio calculated from solubility studies was higher than 250 mL, corresponding to a classification as "not highly soluble." Small, physiological doses of folic acid (≤320 μg) seem to be absorbed completely via active transport, but permeability data f…