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Nýjar aðferðir til að hafa áhrif á frásog og dreifingu lyfja

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Authors
Þorsteinn Loftsson
Issue Date
1993-03-01

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Citation
Læknablaðið 1993, 79(3):96-105
Abstract
The article is a short summary of the authors research efforts for the past few years. It describes some chemical and physicochemical methods which can be used to influence the absorption, distribution and metabolism (elimination), that is the pharmacokinetics, of drugs. Prodrugs are compounds which undergo chemical transformation within the body prior to exhibiting their pharmacological actions. They are obtained by addition of a temporary transport moiety to a known drug molecule. The usage of prodrugs to reduce gastrointestinal irritation (prodrugs of acetylsalicylic acid) and to obtain side specific and sustained drug delivery (chemical delivery systems (pro-prodrugs) of anticancer drugs) is described. Soft drugs are biologically active compounds (drugs) characterised by predictable and controllable metabolism to nontoxic metabolites after they have achieved their therapeutic effect. The design of a soft corticosteroid, loteprednol etabonate, is described. Cyclodextrins are cyclic oligosaccharides with hydrophilic outer surface and a lipophilic cavity in the center. Cyclodextrins are capable of forming inclusion complexes with many drugs by taking up a whole drug molecule, or some part of it, into the cavity. Such encapsulation of a drug molecule will affect many of its physicochemical properties. Cyclodextrins are shown to have effect on the aqueous solubility of drugs and their delivery through biological membranes, e.g. transcorneal delivery of acetazolamide. Also, they can increase both solubility and chemical stability of many anticancer drugs. There are basically two methods which can be used to increase the transdermal delivery of drugs, i.e. by changing the barrier function of the skin and by increasing the availability of drugs at the skin surface. Penetration enhancers, such as oleic acid and lauroylcholine iodide, alter the skin barrier and thereby increase the permeability of drugs into and through the skin. Cyclodextrins do not penetrate the skin barrier. Drug-cyclodextrin complexes deliver drug molecules to the skin surface where they are released before they partition into the skin.
Það er draumur hvers manns sem fæst við rannsóknir í lyfjafræði að uppgötva nýtt lyf en þetta er þó fjarlægur draumur. Reynslan sýnir að af hverjum 9000 nýjum efnasamböndum sem eru samtengd og rannsökuð með tilliti til lyfhrifa verður aðeins eitt að nothæfu lyfi. Mörg lyf og lyfjaflokkar hafa verið uppgötvuð fyrir slysni, eða með einhverjum happa og glappa aðferðum. Á seinni árum hefur verið reynt að þróa aðferðir sem hægt er að beita við hönnun og rannsóknir á nýjum lyfjum (1). Við rannsóknir á nýjum lyfjum hef ég beitt tveimur kerfisbundnum aðferðum til að hafa áhrif á frásog lyfja inn í líkamann, dreifingu þeirra um líkamann og útskilnað þeirra út úr líkamanum. Þessar aðferðir byggjast annars vegar á forlyfjum og hins vegar á mjúkum lyfjum (sjá skilgreiningu á forlyfjum og mjúkum lyfjum síðar í greininni).
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Icelandic Journal Articles (Peer Reviewed)

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