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Because of its Pharmacokinetics of Drug Absorption Dr. Basavaraj K. Nanjwade M. DOI: 10.1007/BF01643430 Corpus ID: 45470296. Im Buch gefunden – Seite 130Pharmakokinetische Interaktionen von Beta-Blockern mit anderen Arzneimitteln Für die Interaktion sind drei Schritte der Pharmakokinetik, nämlich Absorption, Verteilung und Exkretion wichtige Angriffspunkte. Dissolution of the drug inside the body (in vivo) from administered formulation and its transport across the biological membrane are two critical parameters that affect the biopharmaceutical performance of a drug (Maheshwari et al., 2012). During the preclinical and premarketing testing of the drug under study, a great deal of information has been accumulated regarding the doses to be used, the schedule and duration of drug administration, the route of administration, drug absorption, pharmacokinetics, and pharmacodynamics. This article throws light upon the eight main physiological factors that affect the rate of drug absorption. The pharmacokinetics (absorption, distribution, and elimination) of GBE were studied in rats using radiolabeled extracts.2,3,4 After oral administration, at least 60% of the radiolabeled extract was absorbed. how can you talk about this topic and not use that term? Saco de Visser, Hubert Truebel, in Principles of Translational Science in Medicine (Third Edition), 2021. These results suggest that the reduced K a observed was not solely due to longer transit times or reduced motility but other factors are also Pharmacokinetics defines what the body does to the drug. Please support this website by adding us to your whitelist in your ad blocker. Vitamin K epoxide reductase complex genotype 1 (VKORC1). Im Buch gefunden – Seite 3Pharmakokinetische Grundlagen der Dosierung von Neuroleptika unter besonderer Berücksichtigung der Depotneuroleptika ... Im allgemeinen ist die Absorption der geschwindigkeitsbestimmende Schritt für das Auftreten klinischer Wirkungen. There are some drugs that can lead to an increase in the production of the enzyme and as a result speed up the metabolism of the drug and hence a higher dose of the drug is required to achieve the therapeutic effect. Abstract. If you have access to a journal via a society or association membership, please browse to your society journal, select an article to view, and follow the instructions in this box. This deposition pattern, which parallels the circulation improvement observed after ischemia caused by blood clotting in rats, is alleviated by GBE extracts. Clinical pharmacokinetics is the application of pharmacokinetic and pharmacodynamic principles to the safe and effective therapeutic management of an individual patient.. Half-Life Formula. AccessPharmacy is a subscription-based resource from McGraw Hill that features trusted pharmacy content from the best minds in the field. Along with the claims made by Intellipharm™, GastroPlus™ has supplied a more vast software package that can aid developers by, Understanding behavior of drugs in animals and humans, Analyzing the effects of influx and efflux transporters in multiple anatomical tissues, Modeling initial human and animal dosage ranges, tissue metabolism, and targeted tissue concentrations. Gradual uptitration of dose after introduction of metformin or slow release preparations can, in some cases, attenuate symptoms of intolerance . administration or during lymphatic first-pass (e.g. Physicochemical properties of drugs Physical state: liquid form >solid formulation; Lipid -soluble and unionized>water-soluble and ionized form. For example, in older patients with worsening congestive HF syndrome and fluid retention, bowel wall edema may interfere with the absorption of many medications. Die Herausgeber dieses Büchleins sind bzw. waren meine langjährigen Mitarbeiter und haben sich überwiegend mit der praktischen und ange wandten Pharmakokinetik beschäftigt. 3 The 9 5% confidence intervals for the hazard ratios are derived . Foods, especially fat, can slow gastric emptying. Most commonly, a first-order absorption process is used to describe the observed data. Data sources include IBM Watson Micromedex (updated 11 Oct 2021), Cerner Multum™ (updated 1 Nov 2021), ASHP (updated 14 Oct 2021 . Im Buch gefunden – Seite 3Folgende Teilprozesse bestimmen die Pharmakokinetik: 1. Absorption (vom Applikationsort des Medikamentes); 2. Verteilung im Organismus; 3. Metabolismus (Biotransformation); 4. Ausscheidung (Exkretion aus dem Organismus). These genes are detected to determine the use and dosage of this drug for hypercholesterolemia. This enzyme and many other proteolytic enzymes attack the peptide bond that joins the amino acids to make proteins, and in this way break the protein down. permeability, large surface area and high blood flow, the small Matthew MacPherson, ... Srinivas M. Tipparaju, in Artificial Neural Network for Drug Design, Delivery and Disposition, 2016, GastroPlus™ aids in the areas of intravenous, oral, oral cavity, ocular, intranasal, and pulmonary absorption, pharmacokinetics, and pharmacodynamics in human and animals. These genes can affect bleeding, hyper-coagulation and metabolism within the liver. Therefore, gastric Physiological Factors and Drug Absorption | Pharmacokinetics. Pharmacokinetics Basics- Absorption, Distribution, Metabolism and Excretion, Biosynthesis and Regulation of Cholesterol (with Animation), Metabolism of Paracetamol (Acetaminophen), Acetanilide and Phenacetin, Malonic Ester Synthesis – Alkylation of Enolates, A Primer on Measuring Concentrations – Molarity, Moles and Other …, Formulation and Routes of Administration of Drugs, Pharmacognosy and Health Benefits of Capsicum Peppers (Bell Peppers), PK/DB – Database for Pharmacokinetic Properties – IFSC/USP (URL=Â. The deconjugation of the drug by bacterial enzymes is called the enterohepatic cycle. 1 Epinephrine is most commonly administered via intramuscular (IM) The most widely employed extravascular route of Levothyroxine (l-thyroxine) sodium is the sodium salt of the levo isomer of the thyroid hormone thyroxin (T4).Synthetic T4 is chemically identical to that produced in the human thyroid gland. Don't study it, Osmose it. The capillaries in the CNS are different they have pores which are sealed by the connective tissue and hence only small molecules can cross the blood brain barrier and the substances that can cross over have to be very lipophilic in nature. Clin Ther. Lymphatic Drug Absorption via the Enterocytes: Pharmacokinetic Simulation, Modeling, and Considerations for Optimal Drug Development.pdf The regular use of comedication in the target population may require extra drug interaction studies. Niemann–Pick CI Like I (NPCILI) haplotype. (PGp). Durch die j ngste nderung der Approbationsordnung f r Apotheker hat die Bedeutung der Biopharmazie in Forschung und Lehre weiter zugenommen. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, pesticides, food additives, cosmetics, etc. Factors Affecting ADME. The bound drug is inactive and the unbound drug is active. We use cookies to help provide and enhance our service and tailor content and ads. The flavonoids appear to have an affinity for organs rich in connective tissues, such as the aorta, eyes, skin, and lungs. This is especially relevant when considering the dose of the oral nitrate, isosorbide dinitrate (Isordil).4 For example, in this case the dose of isosorbidedinitrate needed to exert the desired pharmacologic effect in an 85-year-old patient is likely to be much less than that required in a 55-year-old patient because more drug is absorbed into the systemic circulation with advancing age owing to decreased first-pass effect. Absorption is the process of delivering a drug into the blood stream. Diseased state can cause a problem on the effectiveness of the drug. Such drugs that metabolized by the liver are said to have a high hepatic first pass. Risks identified were related to patient safety such as cross contamination, suboptimal absorption/pharmacokinetics and inaccurate dose. vitamins. The pharmacokinetic term half-life (t1/2) refers to the time taken for half the initial dose of medicine administered to be eliminated from the body. Keep in mind, however, that there can be a wide variance in response to a given drug among a given population. The degree to which the drug is likely to accumulate in the tissue is dependent on the lipophilicity and local blood flow to the tissue. all these years ive been on 25 mg cortisone acetate and .1 mg fludrocortisone in the am. Im Buch gefunden – Seite 5Pharmakokinetik Dosis eines Arzneistoffes Verteilung Bioverfügbarkeit - Proteinbindung - Blutfluss - Alter - Malabsorption - First pass - Interaktion ( Nahrung , andere Arzneistoffe ) - Alter Bestimmung des Konz . The pharmacokinetics of orally administered drugs may be influenced by feeding. Passage of Drug Molecule Across Membranes 2. pKa 3. pH - pka Partion Concept 4. pH-Partition Hypothesis 5. Finally I’ve This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. for macromolecules The drug travels by some route of administration (oral, topical-dermal, etc.) Im Buch gefunden – Seite 111Vereinfacht kann die Pharmakokinetik durch das LADME-Modell gekennzeichnet werden, das hier vorgestellt werden soll. Die Abkürzung steht für Liberation, Absorption, Distribution, Metabolisierung und Elimination, den Stufen, ... I'm currently doing my PhD at the University of Auckland in the field of cancer biology and bioinformatics. This study investigated the influence of concurrent feeding on fluralaner pharmacokinetics. This chapter describes itraconazole, its nomenclature, formula, physical characteristics, methods of chemical synthesis and analysis, stability, pharmacokinetics, absorption, metabolism, food and drug interaction, and applications. E.g. For a drug even though lipophilic to be absorbed in the intestine some portion of it needs to be dissolved in the intestinal juices which are aqueous. These enzymes modify the drug chemically by processes such as oxidation, reduction and hydrolysis or by the removal and addition of an active group. Damit wird aber auch der Zweck solcher Studien klar: Qualität ist ein relatives Merkmal eines Arzneimittels. Die Validität dieses Merkmals ist immer im Zusammenhang mit dem klinischen Krankheitsbild zu sehen. Of the glands, the adrenals retain the greatest level of radioactivity. Ads are what helps us bring you premium content! absorption, a more absorbable derivative of the drug can be Δdocument.getElementById( "ak_js" ).setAttribute( "value", ( new Date() ).getTime() ); This site uses Akismet to reduce spam. Mike Schachter, in Clinical Pharmacology (Eleventh Edition), 2012. This needs to be done since drugs and chemicals are foreign substances in our body. However, to perform IVIVC, general principles are applied to ensure many factors, such as the proper data supply, enough subject enrollments in IVIVC study, etc., are included in the further discussion. Blood flow: distribution occurs most rapidly into tissues with high blood flow (lungs, kidneys, liver, brain) and least rapidly in tissues with low flow (fat). thyroxine and such drugs can be absorbed into the system by active transport. cefaclor and ceftibuten) are usually better absorbed, with the exception of cefixime. There are some drugs that are completely insoluble in water such drugs float as globules in the intestine but the bile salts will emulsify these into small enough particles such that absorption can take place. MCQS : Pharmacokinetics Question # 1 (Multiple Answer) Concerning oral administration -- disadvantages A) least economical B) drug taken orally may cause emesis C) drug taken orally may be destroyed by gastric acidity D) drug taken orally may be metabolized by gastrointestinal flora E) drug taken orally may be in consistently absorbed due to the presence of food The effects of alteration of gastric pH and food on the pharmacokinetics of 200 mg doses of cefpodoxime proxetil tablets were studied in two separate randomized, open label, crossover studies in healthy subjects. in a chosen dosage form (e.g., tablets, capsules, or in solution). Of the four areas traditionally included in the area of pharmacokinetics, absorption changes in the elderly are probably the least clinically important. 6 Basic pharmacokinetics Cp (a) Time log Cp (b) Time Figure 1.2(a) Plasma concentration (C p) versus time profile of a drug showing a one-compartment model. PubMed ID . Download to read offline. The concentration of drug, drug dissolution, and permeability affects biopharmaceutical performance, hence in vivo performance is estimated by IVIVR using in vitro dissolution data. Factor affecting drugs absorption. Pathology- and age-related physiological changes can also combine to alter oral absorption of medications. Ziel dieser Arbeit war es, mit klinischen Studien und Computersimulationen zur Optimierung von Studien von Bisoprolol bei Kindern beizutragen. intestinal lumen through active transporters such as the P-glycoprotein . The four processes involved when a drug is taken are absorption, distribution, metabolism and elimination or excretion (ADME). easy enough to understand. Prodrug : In order to circumvent incomplete Wow! Because blood levels peaked after 1.5 hours, upper gastrointestinal tract absorption was suspected. degraded by gastric acidity, intestinal membrane enzymes, complexion The biguanide metformin (dimethylbiguanide) is an oral antihyperglycaemic agent widely used in the management of non-insulin-dependent diabetes mellitus (NIDDM). The furosemide pharmacokinetics in healthy volunteers and in patients with renal insufficiency and hepatic cirrhosis is presented. If a basic drug is taken after a meal then the activity of the drug can be reduced whereas if an acidic drug is taken after a meal then the action of the can be noticed much more quickly, owing to the gastric absorption. The clinical relevance is that if the older patient were to be given a larger dose, as is typically used in the younger patient, one would likely see an extension of the desired effect into undesirable effects such as significant orthostatic changes in blood pressure with a subsequent increased risk of falls and fractures. The absorption rate constant has units of inverse time. The sublingual route and to some extent the rectal route can Drug in k 12 k 21 k Central Peripheral Figure 1.3Two-compartment model. This means that the amount of drug that moves from the intestines to the plasma . convenient is the oral route, for some drugs, it allows little read more refers to the processes of drug absorption, distribution, metabolism, and elimination. Hence metabolism deals with making the drug more hydrophilic such that it can be excreted out from the body. By definition, a drug administered intravenously undergoes immediate and complete absorption. The arterial plasma concentrations increased faster than the venous concentrations, with 50% higher maximum concentrations after both intravenous and epidural administration. Pharmacokinetics is the study of a drug absorption, distribution, metabolism and elimination from the body. In turn, it leads to the improvement and development of various theories and models to understand the performance of a drug (Huedo-Medina et al., 2016). Absorption. Wie werden Arzneimittel im Korper verteilt? Several oral dosage forms are available to accommodate the needs of a variety of patients. absorption. In this chapter, ADME profiling in relation to the drug discovery and development process is discussed. e.g. Distribution of Drugs A. Tissue differences in rates of uptake of drugs. GastroPlus™ has recently expanded the ability of their program by including models for in vivo precipitation, in vitro to in vivo extrapolation across all tissues, and updated enzyme and transporter expressions. A physiologically based pharmacokinetic (PBPK) human model for alpelisib, an oral α-specific class I phosphatidylinositol-3-kinase (PI3K) inhibitor, was established to simulate oral absorption and plasma pharmacokinetics of healthy subjects to allow model-informed drug development. Considerable renewal of interest in this drug has been observed in recent years. It show drug effect on body upon administration. A fundamental concept in pharmacokinetics is drug clearance, that is, elimination of drugs from the body, analogous to the concept of creatinine clearance. Im Buch gefunden – Seite 656The pharmacokinetics of the anti- bactrial drugs in carp, trout and catfish is characterised by a retarded absorption and elimination. That is why the single treatment (oral or intramuscular) provides therapeutic concentrations for ... That means that once the free drug enters the target tissue then the protein bound drug will be released to maintain equilibrium. Oral absorption can however be enhanced by galenic formulation for certain drugs. 2016 Sep;38(9):2106-15. doi: 10.1016/j.clinthera.2016.08.003. There are important age-related variations in pharmacokinetics. Variability exists in both pharmacokinetics and pharmacodynamics. administration is the oral route. antihistamines cross the bbb and result in drowsiness, now there are antihistamines that are made that are not so lipophilic in nature. Nevertheless, The hydrophilic group renders the protein soluble in water and the lipophilic compounds are attracted to the lipophilic group and are loosely bound to the protein molecule hence protein bound. They have also updated their software to predict effects in infants. Im Buch gefunden – Seite 226Der Einfluß von Schockzuständen auf die Pharmakokinetik Paumgartner, G. (Med. ... Minderdurchblutung von Darm, Muskulatur, Fettgewebe, Leber und Niere – die Absorption, Verteilung und Elimination von Arzneimitteln beeinflussen können. 12.5 mg cortisone acetate in the pm. 2 The 95% confidence intervals for the hazard ratios are derived from estimates of Cox regression analysis. intestine is the primary site for absorption. The concentration of drug at the desired site is the leading driving force that governs its absorption and deposition in the body. be used to by pass this first-pass effect. anxiolytic benzodiazepines. Nystatin was distributed predominantly in the liver and kidneys following NYT-IL or nystatin parenteral administration, as can be deduced from the AUC values (Table 2).Figures 2 and 3 show nystatin concentrations in liver and kidneys, respectively, as a function of time after NYT-IL . The study evaluate the absorption rate of different sublingual formulation of nitroglycerine (NTG) either in the form of available tablets or a new rapid absorbable gelation capsule formulation "NTG1523" by determining T-max and area under the response curve of nitoglycerine in blood concentration as well as from clinical effects after intake. Epub 2016 Sep 7. Im Buch gefunden – Seite 57044.2· Genetische Polymorphismen im Bereich der Pharmakokinetik Individuelle Wirkung ... Genetische Variabilität findet man auf Seiten der Pharmakokinetik (Absorption, Distribution, Metabolismus und Elimination) eines Medikaments sowie ... which also limits their absorption (even when intestinal uptake is Safe Weighing Range Ensures Accurate Results. One question can be concealed in several studies, and one study can provide partial answers to multiple questions. For a typical drug, one standard deviation in the values observed for bioavailability (F), clearance (CL) and volume of distribution (Vd) would be about 20%, 50% and 30% respectively. and in a specific dosage form such as a tablet, capsule, solution and so on.. Im Buch gefunden – Seite 139Die Pharmakokinetik beschreibt den Prozess, durch den Wirksub- stanzen in den Körper aufgenommen, im Körper verteilt, verstoffwechselt und wieder ausgeschieden werden. Für diese Prozesse steht die Abkürzung ADME: ADME ̆ Absorption der ... With furosemide (Lasix), for example, the extent of absorption is not affected, but the rate of absorption is slowed, which can lead to a diminished clinical efficacy.5 Recognition of this physiologic blockade to the desired effect is critical as it will avoid needless delays in obtaining the desired effect by giving furosemide via a parenteral route. i have been looking into pharmacokinetics as a possible lead to the next solution. the stomach where it usually disintegrates and dissolves in the gastric Additionally, different strategies to accelerate lead finding and lead optimization processes has shifted the chemical libraries towards poorer biopharmaceutical properties. Both can be used for detection of platelet reactivity in relationship to thrombotic and bleeding events. Twelve fasted or fed beagles received a single oral administration of 25 mg fluralaner/kg body . Several decades passed with substantial efforts by pharmaceutical scientists to correlate in vitro dissolution of drug data with in vivo pharmacokinetics (absorption, distribution, metabolism, and excretion) of the drugs (Choudhury et al., 2017). The pharmacokinetic properties determine the onset, intensity, and the duration of drug action in body. Im Buch gefunden – Seite 12Pharmakokinetik – Der Begriff umfasst die Absorption, Distribution, Metabolisierung und Exkretion von Medikamenten (ADME). Pharmakodynamik – Der Begriff beschreibt die Wirkungen der Medikamente auf den Organismus und deren ... Some of the drugs are similar to compounds found in the body for e.g. Some drugs are further metabolized as a consequence of hepatic first-pass effect, sulphates and glucuronide. Peak Action: occurs when the drug reaches its highest blood or plasma concentration. 2. Physikalisch-chemische Eigenschaften von Buspiron . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3. are completely absorbed unless destruction occurs at the site of The oral absorption of the loop diuretic, torsemide (Demedex), in HF syndrome patients with worsening left ventricular failure has been shown to be more predictably absorbed with improved clinical outcome when compared to furosemide.6, Om Silakari, Pankaj Kumar Singh, in Concepts and Experimental Protocols of Modelling and Informatics in Drug Design, 2021. Da es wenige fundierte populationspharmakokinetische Studien zu Indomethacin insgesamt und nur eine bei Kindern gibt, sollte in der hier vorliegenden Arbeit die Populationspharmakokinetik von Indomethacin bei Kindern mit ... This genotype is detected to determine the clinical benefit of this drug. These terms were first presented together in English by Nelson in 1961, rephrasing resorption, distribution, consumption and elimination used by Teorell in 1937 [Nelson, 1961; Teorell, 1937].Other relevant seminal works include Widmark's description of . Absorption is the process of delivering a drug into the blood stream. By contrast, drugs administered extravascularly need to be carried through various barriers in order to be able to reach the blood circulation and then their site of action. lumen. HST-151 4 II. Absorption is the journey of a drug travelling from the site of administration to the site of action.. The drug travels by some route of administration (oral, topical-dermal, etc.) If two drugs bind at the same site of the protein and are administered together then there can be problems. Levels of radioactivity in these tissues are two to three times higher than those in blood and decrease little over time. Associated with these variances in response within a given population is the variance in dose needed to provide therapeutic benefit in a given member of that population and a dose that can cause an ADR in that individual. Im Buch gefundenPharmakokinetische Eigenschaften lassen sich nach dem LADME-Prinzip untergliedern: L: Liberation (Freisetzung aus der Verabreichungsform) A: Absorption (auch „Resorption“, Aufnahme vom Applikationsort in die Blutbahn) D: Distribution ... essential step in absorption and is influenced by the physicochemical 🙂, having had addisons disease for 33 years, having led a normal life wo any addisons problems which require stress dosing, or hospital stays, i now find myself unable to work or do much of any activity. Lipid soluble non – ionized drugs are absorbed faster. 2 | DRETCHE ET AL. orally, rectally, intra-muscularly, subcutaneously, inhalation, topically, etc.). Essential Laboratory Skills Guide. Read chapter 8 of Applied Biopharmaceutics & Pharmacokinetics, 7e online now, exclusively on AccessPharmacy. intestine (2-4 hours). Im Buch gefunden – Seite 87Im Folgenden wird ein kurzer Überblick über Resorption, Bioverfügbarkeit und sonstige pharmakokinetische Eigenschaften von ... 87 Exposition und Pharmakokinetik 4.2 Exposition Pharmakokinetik Exposition Absorption, Resorption, Verteilung. The random walk method is particularly useful for predicting complex processes such as repeated topical application of a drug. Itraconazle is an antifungal given by mouth for the treatment of aropharyngeal and vulvogaginal candidiasis, for pityriasis versicolor, for dermatophytosis unresponsive to topical treatment, for mychomycosis, and for systemic infections, including aspergillosis, blastomycosis, candidiasis, chromoblastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, paracoccidioidomycosis, and sparotrichosis. Bowel length and effective absorptive surface. Itraconazole is slowly but well absorbed after oral administration with peak concentrations reached in approximately 4 h. Absorption is enhanced in the presence of food and in acidic intragasic environment. emptying is an important factor influencing the rate of drug absorption. Passage of Drug Molecule Across Membranes 2. pKa 3. pH - pka Partion Concept 4. pH-Partition Hypothesis 5. After absorption most drugs are distributed in the blood to the body tissue where they have their effect. its low permeability and relatively low surface area. When drugs are injected into the muscle, subcutaneous layer absorption still has to take place but it is less dependent on the chemical nature of the drugs since the drugs are absorbed into the circulatory system through the small pores in the capillary walls. This effect is not seen with isosorbide mononitrate (Imdur). glucose dehydrogenase. All the four processes involve drug movement across the membranes. Im Buch gefunden – Seite 30621.1 Grundzüge der Pharmakokinetik und Pharmakodynamik Die wirksame Konzentration eines Pharmakons wird durch ihr ... Die Absorption von Arzneimitteln ist abhängig von der Funktion des MagenDarm - Traktes und von evtl. gleichzeitig ... I have done a MSc in Pharmacology from The University of Auckland. Abdullah A. Al-Badr, Hussein I. El-Subbagh, in Profiles of Drug Substances, Excipients and Related Methodology, 2009. If the drug continues to be in the lipohilic state and is going to be filtered by the glomerulus then it will be reabsorbed and remain in the body for prolonged periods.

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