In Vitro and In Vivo Tests in Cutaneous Adverse Drug Reactions

2018 ◽  
pp. 247-263
Author(s):  
Annick Barbaud
Keyword(s):  
Adverse Drug Reactions ◽  
Drug Reactions ◽  
In Vivo Tests

Abstract 229: Correlation of in vitro Studies and Human Drug Interaction Studies with Gemcabene

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Margaret McShane ◽  
Louis Radulovic ◽  
Charles L Bisgaier
Keyword(s):  
Drug Interaction ◽  
Drug Interactions ◽  
Adverse Drug Reactions ◽  
Multiple Dose ◽  
Drug Reactions ◽  
Open Label ◽  
Transport Pathways ◽  
Dose Study

Background: Gemcabene is a novel lipid-regulating compound being developed as an adjunct to diet and statin therapy for dyslipidemia treatment. Patients with dyslipidemia typically take many medications often including statins and it is essential to understand potential risk of drug-drug interactions (DDI) to minimize the risk of adverse drug reactions. In the best circumstances, drugs entering the market will provide metabolic or transport pathways that do not interfere with commonly co-administered drugs. The current studies provide the analysis of potential drug interactions with gemcabene both in vitro and in vivo . Methods: Caco-2 cells were used to assess the potential P-gp substrate and inhibitor interaction and the major drug-metabolizing CYP450 isozymes and FMO-3 were used to assess the potential CYP450 and FM0-3 metabolism interaction. The results from the in vitro P-gp and CYP450 studies was correlated with the results of three DDI clinical studies with digoxin, atorvastatin and simvastatin. Results: In an open-label, multiple-dose study in 12 healthy subjects, gemcabene (900 mg) did not significantly affect the exposure (Cmax and AUC 0-24 ) of digoxin (0.25 mg). Specifically, the 90% confidence interval for digoxin AUC (0-24) ratios were within the 80% to 125% range, thus confirming the in vitro results of no DDI with a P-gp substrate. In two open-label, multiple-dose studies in healthy volunteers, gemcabene (900 mg) did not significantly affect the exposure (Cmax and AUC 0-24 ) of atorvastatin (80 mg) or simvastatin (80 mg) thus confirming the in vitro results of no DDI with CYP450 (see Figure below). Conclusion: These results suggest gemcabene is unlikely to elicit a metabolic (i.e., CYP450 or FMO3) or P-gp-mediated drug interaction. Gemcabene (900 mg) was well-tolerated in combination with highest dose of atorvastatin and simvastatin. Clinical Implications: Understanding potential for drug interactions minimizes the risk of adverse drug reactions.

In Vitro Methods as a Tool in Neurotoxicity Studies

1995 ◽  
Vol 23 (4) ◽  
pp. 491-496
Author(s):  
Hanna Tähti ◽  
Leila Vaalavirta ◽  
Tarja Toimela
Keyword(s):  
Risk Evaluation ◽  
Toxicity Testing ◽  
In Vitro Models ◽  
In Vitro Tests ◽  
Industrial Chemicals ◽  
Mercury Compounds ◽  
Toxicological Data ◽  
In Vivo Tests

— There are several hundred industrial chemicals with neurotoxic potential. The neurotoxic risks of most of these chemicals are unknown. Additional methods are needed to assess the risks more effectively and to elucidate the mechanisms of neurotoxicity more accurately than is possible with the conventional methods. This paper deals with general tasks concerning the use of in vitro models in the evaluation of neurotoxic risks. It is based on our previous studies with various in vitro models and on recent literature. The induction of glial fibrillary acidic protein in astrocyte cultures after treatment with known neurotoxicants (mercury compounds and aluminium) is discussed in more detail as an important response which can be detected in vitro. When used appropriately with in vivo tests and with previous toxicological data, in vitro neurotoxicity testing considerably improves risk assessment. The incorporation of in vitro tests into the early stages of risk evaluation can reduce the number of animals used in routine toxicity testing, by identifying chemicals with high neurotoxic potential.

scholarly journals Role of in vitro and in vivo tests of hypersensitivity in beryllium workers.

1977 ◽  
Vol 30 (1) ◽  
pp. 24-28 ◽  
Author(s):  
C D Price ◽  
W J Williams ◽  
A Pugh ◽  
D H Joynson
Keyword(s):  
In Vivo Tests

scholarly journals Essential Oils and Their Bioactive Compounds in the Control of Gastrointestinal Nematodes of Small Ruminants

2018 ◽  
Vol 46 (1) ◽  
pp. 14 ◽  
Author(s):  
Weibson Paz Pinheiro André ◽  
Wesley Lyeverton Correia Ribeiro ◽  
Lorena Mayana Beserra de Oliveira ◽  
Iara Tersia Freitas Macedo ◽  
Fernanda Cristina Macedo Rondon ◽  
...  
Keyword(s):  
Natural Products ◽  
Essential Oils ◽  
Bioactive Compounds ◽  
Small Ruminant ◽  
Anthelmintic Activity ◽  
Gastrointestinal Nematodes ◽  
In Vivo Tests ◽  
Anthelmintic Effect

Background: Gastrointestinal nematodes are one of the major health and economic problem of sheep and goats in the world. The control of these nematodes is carried out conventionally with synthetic anthelminths, which favored the selection of gastrointestinal nematode (GIN) populations multiresistant to anthelmintics. The emergence of anthelmintic resistance has stimulated the search for new alternatives to control small ruminant GIN, standing out the use of plants and their bioactives compounds, such as essential oils (EO). The objective of this review was to present the main characteristics and anthelmintic activity of EO, their isolated compounds and drug delivery systems in the control of GIN.Review: Essential oils are a complex blend of bioactive compounds with volatile, lipophilic, usually odoriferous and liquid substances. EO are composed of terpenes, terpenoids, aromatic and aliphatic constituents. EO has various pharmacological activities of interest in preventive veterinary medicine such as antibacterials, antifungals, anticoccicids, insecticides and anthelmintics. In vitro and in vivo tests are used to validate the anthelmintic activity of EO on GIN. In vitro tests are low cost screening tests that allow the evaluation of the anthelmintic activity of a large amount of bioactive compounds on eggs, first (L1) and third stage larvae (L3), and adult nematodes. The antiparasitic effect of EO is related to its main compound or to the interaction of the compounds. These bioactive compounds penetrate the cuticle of the nematodes by transcuticular diffusion, altering the mechanisms of locomotion, besides causing cuticular lesions. Following in vitro evaluation, the acute and sub-chronic toxicity test should be performed to assess the toxicity of the bioactive compounds and to define the dose to be used in in vivo tests. In vivo tests are more reliable because the anthelmintic effectiveness of bioactive compounds is evaluated after the metabolization process. The metabolization process of the bioactive compounds can generate metabolites that exhibit or not anthelmintic effectiveness. The in vivo tests assessing the anthelmintic effectiveness of bioactive compounds in sheep and goats are the fecal egg count reduction test and the controlled test.  OE promoted reduction of egg elimination in faeces which may be related to cuticular and reproductive alterations in GIN, and reduction of parasite burden in in vivo tests. Due to the promising results obtained with OE in the in vivo tests, interest has been aroused in using nanotechnology as an alternative to increase the bioavailability of OE and consequently, potentializing its anthelmintic effect, reducing the dose and  toxicity of the biocompounds. In addition to nanotechnology, the isolation and chemical modification of compounds isolated from OE have been employed to obtain new molecules with anthelmintic action and understand the mechanism of action of EO on the small ruminant GIN.Conclusion: The use of EO and their compound bioactive in the control of resistant populations of GIN is a promising alternative. The adoption of strategies in which natural products can replace synthetic anthelmintics, such as in dry periods and use synthetic anthelmintics in the rainy season when the population in refugia in the pasture is high, thus reducing the dissemination of GIN resistant populations. As perspective, the evaluation of pharmacokinetics and pharmacodynamics of these natural products should be performed so that one defines treatment protocols that optimize the anthelmintic effect.

scholarly journals Polymyxins Nebulization over Intravenous Injection: Pharmacokinetics and Pharmacodynamics-Based Therapeutic Evaluation

2019 ◽  
pp. 1-10
Author(s):  
Md. Jahidul Hasan
Keyword(s):  
Respiratory Tract ◽  
Adverse Drug Reactions ◽  
Intravenous Administration ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Drug Reactions ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Gram Negative ◽  
Tract Infections

Polymyxins are the last line potential antibiotics against multi-drug resistant gram-negative bacteria and consist of two sister antibiotics: Polymyxin B and colistin (polymyxin E). Intravenous use of polymyxins was started from a long ago in the treatment of serious gram-negative infections and once their uses were restricted due to potential adverse drug reactions, such as nephrotoxicity and neurotoxicity. Lack of in vivo clinical studies on polymyxins mostly, in human body makes the pharmacokinetics and pharmacodynamics of polymyxin B and colistin unclear in many aspects, such as the distribution of polymyxins in different compartments of lung. The nebulization of polymyxins is practicing very limitedly and lack of clinical evidence has not justified this administration technique yet properly to date. The main objective of this review study was to evaluate the pharmacokinetic and pharmacodynamic properties of intravenous and nebulized polymyxins and the related therapeutic potentialities. Aerosolized polymyxins directly administered to the respiratory tract was found with higher drug concentration in different subcompartments of lungs than the intravenous administration and sustainably meets the minimum inhibitory concentration locally with superior bactericidal properties in respiratory tract infections. In contrast, intravenous administration of polymyxins shows similar anti-infective superiority in other organs, such as blood, urinary tract etc. So, during this alarming situation of rapidly emerging multidrug-resistant organisms in human communities, therapeutic administration techniques of last resort polymyxins should be clinically evidence-based for achieving optimum therapeutic outcomes with minimum chance of adverse drug reactions.  

Calcification Modelling in Artificial Heart Valves

1992 ◽  
Vol 15 (5) ◽  
pp. 284-288 ◽  
Author(s):  
A.C. Fisher ◽  
G.M. Bernacca ◽  
T.G. Mackay ◽  
W.R. Dimitri ◽  
R. Wilkinson ◽  
...  
Keyword(s):  
Artificial Heart ◽  
Heart Valves ◽  
Test Protocol ◽  
Tissue Sections ◽  
Artificial Heart Valves ◽  
In Vivo Tests ◽  
Tissue Contents ◽  
Histological Staining

This study has examined a range of methods of studying the calcification process in bovine pericardial and polyurethane biomaterials. The calcification methods include static and dynamic, in vitro and in vivo tests. The analytical methods include measurement of depletion rates of calcium and phosphate from in vitro calcifying solutions, analysis of tissue contents of calcium, histological staining of tissue sections for calcium, X-ray elemental analysis, by scanning electron microscopy, of calcium and phosphorus distributions over valve leaflets calcified in vitro under dynamic conditions. Bovine pericardium, in all test settings, calcified to a much greater degree than polyurethane biomaterials. Polyurethane extracts calcified to a greater degree than bulk polyurethanes. The test protocol used allows progress through increasily demanding calcification tests, with the possibility of eliminating unsuitable materials with tests of limited complexity and expense.

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