Search results for "PHARMACOKINETICS"

In vivo comparison of DOTA based 68Ga-labelled bisphosphonates for bone imaging in non-tumour models.

2013

Bone metastases are a class of cancerous metastases that result from the invasion of a tumor into bone. The solid mass which forms inside the bone is often associated with a constant dull ache and severe spikes in pain, which greatly reduce the quality of life of the patient. Numerous (99m)Tc-labeled bisphosphonate functionalised complexes are well established tracers for bone metastases imaging. The objective of this research was to evaluate the pharmacokinetics and behaviour of three DOTA based bisphosphonate functionalised ligands (BPAMD, BPAPD and BPPED), using both (68)Ga μ-PET in vivo imaging and ex vivo biodistribution studies in healthy Wistar rats. The compounds were labelled with …

Pharmacological distribution diagrams: a tool for de novo drug design.

1996

Abstract Discriminant analysis applied to SAR studies using topological descriptors allows us to plot frequency distribution diagrams: a function of the number of drugs within an interval of values of discriminant function vs. these values. We make use of these representations, pharmacological distribution diagrams (PDDs), in structurally heterogeneous groups where generally they adopt skewed Gaussian shapes or present several maxima. The maxima afford intervals of discrimianant function in which exists a good expectancy to find new active drugs. A set of β-blockers with contrasted activity has been selected to test the ability of PDDs as a visualizing technique, for the identification of n…

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Sitagliptin Phosphate Monohydrate

2021

Sitagliptin is an antihyperglycemic drug used in adults for the treatment of diabetes Type 2. Literature data and in-house experiments were applied in this monograph to assess whether methods based on the Biopharmaceutics Classification System (BCS) could be used to assess the bioequivalence of solid immediate-release (IR) oral dosage forms containing sitagliptin phosphate monohydrate, as an alternative to a pharmacokinetic study in human volunteers. The solubility and permeability characteristics of sitagliptin were reviewed according to the BCS, along with dissolution, therapeutic index, therapeutic applications, pharmacokinetics, pharmacodynamic characteristics, reports of bioequivalence…

Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Ketoprofen

2012

Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing ketoprofen are reviewed. Ketoprofen's solubility and permeability, its therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability (BA)/dissolution data were taken into consideration. The available data suggest that according to the current Biopharmaceutics Classification System (BCS) and all current guidances, ketoprofen is a weak acid that would be assigned to BCS Class II. The extent of ketoprofen abso…

Pharmacokinetics of oligodeoxynucleotides encapsulated in liposomes: effect of lipid composition and preparation method

2000

1. The effect of the method employed to prepare liposomes and their lipid composition were evaluated in terms of the encapsulation efficiency and pharmacokinetic features of two oligodeoxynucleotides of a 21 mer: the normal (N-Odn) and the phosphorothioate (S-Odn) oligodeoxynucleotide. 2. Liposomes were prepared by the classical method of multilamellar vesicles (MV) and by the dehydration-rehydration method (DR). Two lipid mixtures were used to prepare liposomes--the predominant lipid being phosphatidylcholine (PC) and sphingomyelin (SM) respectively. 3. The DR method for liposome preparation provided the highest encapsulation efficiency, regardless of liposome lipid composition and the typ…

A survey on IVIVC/IVIVR development in the pharmaceutical industry – Past experience and current perspectives

2017

The present work aimed to describe the current status of IVIVC/IVIVR development in the pharmaceutical industry, focusing on the use and perception of specific approaches as well as successful and failed case studies. Two questionnaires have been distributed to 13 EFPIA partners of the Oral Biopharmaceutics Tools Initiative and to the Pharmacokinetics Working Party of the European Medicines Agency in order to capture the perspectives and experiences of industry scientists and agency members, respectively. Responses from ten companies and three European Agencies were received between May 21st 2014 and January 19th 2016. The majority of the companies acknowledged the importance of IVIVC/IVIVR…

Cross‐sectional comparative study of pharmacokinetics and efficacy between sucrose‐formulated recombinant factor VIII (Kogenate ® ) and BAY 81‐8973 (…

2019

Biopartitioning micellar chromatography: an in vitro technique for predicting human drug absorption.

2001

The main oral drug absorption barriers are fluid cell membranes and generally drugs are absorbed by a passive diffusion mechanism. Biopartitioning micellar chromatography (BMC) is a mode of micellar liquid chromatography that uses micellar mobile phases of Brij35 under adequate experimental conditions and can be useful to mimic the drug partitioning process in biological systems. In this paper the usefulness of BMC for predicting oral drug absorption in humans is demonstrated. A hyperbolic model has been obtained using the retention data of a heterogeneous set of 74 compounds, which shows predictive ability for drugs absorbed by passive diffusion. The model obtained in BMC is compared with …

The Influence of Single-Dose and Short-Term Administration of Quercetin on the Pharmacokinetics of Midazolam in Humans.

2015

Quercetin is a plant flavonol that is available from both daily diet and nutraceuticals. To investigate the effect of acute and short-term intake of high-dose quercetin on CYP3A-mediated metabolism, 10 healthy volunteers received 7.5 mg oral midazolam without, with a single dose of 1500 mg quercetin and after 1-week supplementation with 1500 mg quercetin daily. A substudy was performed in three subjects to explore the impact of repeated quercetin intake on intravenously administered midazolam. Coadministration with a single dose of quercetin did not significantly alter the pharmacokinetics of midazolam and its 1'-hydroxymetabolite, but following short-term quercetin intake, there was a tren…

Influence of concomitant medications on the total clearance and the risk for supra-therapeutic plasma concentrations of Citalopram. A population-base…

2014

Introduction: The main objective of this study was to investigate the influence of the use of multiple medications and other risk factors on citalopram plasma concentrations. Methods: A retrospective cohort study with a naturalistic population of 957 patients for whom routine therapeutic drug monitoring (TDM) of citalopram had been requested between 2006 and 2013 was conducted. Results: Concomitant drugs inhibiting at least 2 different CYP subtypes involved in the metabolism of citalopram decreased statistically significantly the total clearance (Clt). Compared to younger patients over 64-year-old patients had on average a 4.5 times higher risk rate of supra-therapeutic plasma concentration…