Search results for "Valency"
showing 10 items of 70 documents
Hyperalgesia and opioid switching
2005
Opioids, intended to abolish pain, can unexpectedly produce hyperalgesia, particularly during rapid opioid escalation. Opioid switching could be a therapeutic option in a condition of opioid-induced tolerance or hyperalgesia, but conversion ratios between opioids are difficult to apply in this context and require strict surveillance and expertise. This situation is challenging, because the rapid escalation of opioid doses, possibly due to the development of opioid-induced tolerance, can cause hyperalgesia. To avoid this adverse effect, clinicians need to refine their assessment of pain treatment and consider opioid switching. The authors present a case report in which switching from fentan…
Effect of the preparation method and grinding time of some mixed valency ferrite spinels on their cationic distribution and thermal stability toward …
1996
Abstract The reactivity in oxygen of several mixed valency ferrite spinels, namely Fe3O4, FeCr2O4, Fe3 − xTixO4 and Fe3 − xMoxO4 was investigated by derivative thermogravimetry (DTG) analysis as a function of the conditions of preparation and grinding. For all these compounds, low temperature preparation or prolonged grinding time enables small particles ( 0.5 μm), it was observed that oxidation was starting at higher temperature and that the defect spinel phases could not be retained during oxidation. This behaviour was attributed to the presence of stresses induced by the lattice parameter gradient and promoting the formation of nuclei of the α-rhombohedral phase from the superficial γ-de…
Medroxyprogesterone acetate: steady-state pharmacokinetics bioequivalence of two oral formulations
1989
Two micronized oral formulations of medroxyprogesterone acetate (MPA) (Farlutal and Clinovir) were compared in order to evaluate their relative bioavailability. Sixteen female patients with metastatic breast cancer were entered in a randomized cross-over study on 500-mg MPA tablets repeatedly administered (twice daily for 20 days). At the steady state, similar mean +/- SD serum levels of MPA were obtained (131 +/- 44 ng/ml for Farlutal and 136 +/- 45 ng/ml for Clinovir) and the two formulations proved to be bioequivalent (confidence interval at a significance level of 0.95 = 93%-107%).
Picomolar inhibition of cholera toxin by a pentavalent ganglioside GM1os-calix[5]arene
2013
Cholera toxin (CT), the causative agent of cholera, displays a pentavalent binding domain that targets the oligosaccharide of ganglioside GM1 (GM1os) on the periphery of human abdominal epithelial cells. Here, we report the first GM1os-based CT inhibitor that matches the valency of the CT binding domain (CTB). This pentavalent inhibitor contains five GM1os moieties linked to a calix[5]arene scaffold. When evaluated by an inhibition assay, it achieved a picomolar inhibition potency (IC50 = 450 pM) for CTB. This represents a significant multivalency effect, with a relative inhibitory potency of 100000 compared to a monovalent GM1os derivative, making GM1os-calix[5]arene one of the most potent…
Pharmacy and pharmacology of biosimilars
2008
Biosimilar medicines are biological medicinal products that can obtain a marketing authorization in the EU after the original product (biological reference medicine) has run out of patent. As a prerequisite, studies including clinical trials are to be conducted to compare the quality, safety, and efficacy of the biosimilar and reference medicine. Due to the specific characteristics of biopharmaceuticals like complex 3-dimensional (glyco) protein structure, immunogenicity, production in living organisms, which causes heterogeneity, complex manufacturing process and analysis, interchangeability of the biosimilar with its reference drug product is not guaranteed. In addition, INN (internationa…
Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Ondansetron.
2019
Literature data pertaining to the physicochemical, pharmaceutical, and pharmacokinetic properties of ondansetron hydrochloride dihydrate are reviewed to arrive at a decision on whether a marketing authorization of an immediate release (IR) solid oral dosage form can be approved based on a Biopharmaceutics Classification System (BCS)-based biowaiver. Ondansetron, a 5HT3 receptor antagonist, is used at doses ranging from 4 mg to 24 mg in the management of nausea and vomiting associated with chemotherapy, radiotherapy, and postoperative treatment. It is a weak base and thus exhibits pH-dependent solubility. However, it is able to meet the criteria of "high solubility" as well as "high permeabi…
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…
Risk analysis in bioequivalence and biowaiver decisions
2013
This article evaluates the current biowaiver guidance documents published by the FDA, EU and WHO from a risk based perspective. The authors introduce the use of a Failure Mode and Effect Analysis (FMEA) risk calculation tool to show that current regulatory documents implicitly limit the risk for bioinequivalence after granting a biowaiver by reduction of the incidence, improving the detection and limiting the severity of any unforeseen bioinequivalent product. In addition, the authors use the risk calculation to expose yet unexplored options for future extension of comparative in vitro tools for biowaivers.
Normalización del intercambio terapéutico de antagonistas del receptor de la angiotensina-II para el tratamiento de la hipertensión en el medio hospi…
2005
Resumen Introduccion La normalizacion del proceso de intercambio terapeutico de medicamentos en el medio hospitalario, mediante el establecimiento y difusion de criterios normalizados, se ha definido como una actividad que conduce a un incremento en la calidad asistencial y, consecuentemente, a una mejora en el cuidado del paciente. Objetivo Establecer un intercambio terapeutico normalizado para los antagonistas del receptor de angiotensina-II (ARA-II) en el tratamiento de la hipertension arterial y, evaluar la idoneidad de los intercambios terapeuticos realizados en un sistema integral de dispensacion individualizada de medicamentos. Material y metodos El intercambio terapeutico normalizad…
Bioequivalence of oral products and the biopharmaceutics classification system: science, regulation, and public policy.
2011
The demonstration of bioequivalence (BE) is an essential requirement for ensuring that patients receive a product that performs as indicated by the label. The BE standard for a particular product is set by its innovator, and this standard must subsequently be matched by generic drug products. The Biopharmaceutics Classification System (BCS) sets a scientific basis for an improved BE standard for immediate-release solid oral dosage forms. In this paper, we discuss BE and the BCS, as well as the issues that are currently relevant to BE as a pharmaceutical product standard.