Search results for "PHARMACOKINETICS"
showing 10 items of 458 documents
Status of Recombinant Factor VIII Concentrate Treatment for Hemophilia A in Italy: Characteristics and Clinical Benefits
2019
The current interest in recombinant factor VIII (rFVIII) products stems from the fact that they offer a technological solution to prolonging the half-life of and reducing the risk of formation of alloantibodies (inhibitors) against FVIII in treated patients with hemophilia A (HA). The Italian health care system has authorized the use of a wide range of rFVIII concentrates of the first, second, and third generation, as well as new innovative rFVIII preparates with an extended half-life (EHL) (Kogenate FS®-Bayer, belonging to the second generation and replaced since 2017 by a product consisting of the same modified molecule; because it is only available until the end of the current year, it w…
Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography.
1999
The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly hydrophobicity and molar total charge) also control the pharmacokinetic and biochemical behavior. Micellar liquid chromatography (MLC) has been proposed to emulate in vitro the partitioning process in the biomembranes. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of …
A mathematical approach to predicting the percutaneous absorption enhancing effect of sodium lauryl sulphate.
2003
A study has been made of the effect of sodium lauryl sulphate (SLS) at several concentrations from 0.24 to 5% (w/w) on skin permeability. Seven model drugs were selected for this study on the basis of their lipophilicity as represented by their logP(oct) values (from -0.95 to 4.2). Skin pre-treatment with aqueous solutions of SLS does not increase the permeability coefficient of the most lipophilic compounds (logP(oct)> or =3). For the other compounds assayed the increase in the permeability coefficients depends on the concentration of SLS used in the skin pre-treatment, and on the lipophilicity of the compounds tested.The correlation between the inverse of SLS efficacy as an enhancer (1/ER…
Pyrrolomycins as antimicrobial agents. Microwave-assisted organic synthesis and insights into their antimicrobial mechanism of action
2019
Abstract New compounds able to counteract staphylococcal biofilm formation are needed. In this study we investigate the mechanism of action of pyrrolomycins, whose potential as antimicrobial agents has been demonstrated. We performed a new efficient and easy method to use microwave organic synthesis suitable for obtaining pyrrolomycins in good yields and in suitable amount for their in vitro in-depth investigation. We evaluate the inhibitory activity towards Sortase A (SrtA), a transpeptidase responsible for covalent anchoring in Gram-positive peptidoglycan of many surface proteins involved in adhesion and in biofilm formation. All compounds show a good inhibitory activity toward SrtA, havi…
Detoxifying antitumoral drugs via nanoconjugation: the case of gold nanoparticles and cisplatin
2021
Nanoparticles (NPs) have emerged as a potential tool to improve cancer treatment. Among the proposed uses in imaging and therapy, their use as a drug delivery scaffold has been extensively highlighted. However, there are still some controversial points which need a deeper understanding before clinical application can occur. Here the use of gold nanoparticles (AuNPs) to detoxify the antitumoral agent cisplatin, linked to a nanoparticle via a pH-sensitive coordination bond for endosomal release, is presented. The NP conjugate design has important effects on pharmacokinetics, conjugate evolution and biodistribution and results in an absence of observed toxicity. Besides, AuNPs present unique o…
Topiramate pharmacokinetics in neonates undergoing therapeutic hypothermia and proposal of an optimised dosing schedule.
2019
Aim The adequate dosing of topiramate in neonates undergoing therapeutic hypothermia has not been established. The aim of this study was to design a dosing schedule capable of providing topiramate serum concentrations within the accepted therapeutic range. Methods Neonates (n = 52) with hypoxic ischaemic encephalopathy and subjected to therapeutic hypothermia were dosed with topiramate, 5 mg/kg on day one and 3 mg/kg on days two to five, to decrease seizure events. A total of 451 topiramate serum concentrations obtained in the patients were used to develop a population pharmacokinetic model using a non-linear mixed-effects modelling approach. Results A one-compartment model with first-order…
Impact of Undernourishment on the Pharmacokinetics of Erlotinib and Gefitinib in Rats
2017
The relationship between nutritional status and pharmacokinetics has been previously studied for classical anticancer drugs, but this relationship remains unexplored for modern therapies involving targeted drugs and new administration routes. In this context, the main objective of this thesis was to evaluate, in undernourished and well-nourished Wistar rats, the impact of undernourishment on the pharmacokinetics of erlotinib and gefitinib, two novel orally administered targeted-drugs. The research investigation was divided into three main experiments: • Evaluation of analytical and molecular alterations associated with undernourishment • In situ intestinal perfusion studies • In vivo pharma…
Comparison of analgesic effects of intravenous and intranasal ketorolac in patients with mandibular fracture-A Randomized Clinical Trial
2019
Background Similarity of pharmacokinetics of intranasal ketorolac to the intravenous form and other advantages have promoted its application. This study compared the analgesic effects of intravenous and intranasal ketorolac in patients undergoing mandibular fracture surgery. Material and Methods In this clinical trial study, Sixty-four patients with unilateral mandibular fracture were divided randomly into two groups. In group 1, 30 mg of intravenous (IV) ketorolac was injected every 8 hours and in group 2, intranasal (IN) ketorolac spray was used as a 100-µL puff in each nostril (31.5 mg) every 6 hours. After each patient regained consciousness, pain intensity was measured based on visual …
Vitamin A in parenteral nutrition: uptake and distribution of retinyl esters after intravenous application.
1989
Short-term parenteral application of vitamin A was examined in rats. Retinyl margarinate, which is chemically similar to physiological retinyl esters, was used in vitamin A-depleted rats to study uptake, distribution, and storage of retinyl esters in tissues. Vitamin A-depleted and Vitamin A-sufficient rats were infused with a micellar suspension of retinyl margarinate for 7 h and then killed at different times. Retinyl margarinate was directly taken up by all tissues examined. It appears that infusion of retinyl esters in micellar form provides a direct way to supply vitamin A to peripheral, vitamin A-dependent tissues. Therefore, a short-term infusion of retinyl esters with an emulsifier …
Age-dependent differences in the effect of phenprocoumon on the vitamin K1-epoxide cycle in rats
1980
Abstract The anticoagulant activity and the pharmacokinetics of phenprocoumon as well as the effect of phenprocoumon on the vitamin K1-epoxide cycle in younger (12 weeks) and older (36 weeks) male inbred Lewis rats has been examined in a study of the mechanism responsible for the increase in the responsiveness to oral anticoagulant drugs (OAD's) with increasing age. After a single i.v.-dose of phenprocoumon (0†355 mg kg−1 the anticoagulant effect obtained was greater in older than in younger rats. There were no differences between younger and older rats in the rate of elimination, volume of distribution and in the free fraction and free concentration values of phenprocoumon in plasma and li…