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1. 1. P-glycoprotein and chiral antidepressant drugs : Pharmacokinetic, pharmacogenetic and toxicological aspects

   Författare :Louise Karlsson; Fredrik C. Kugelberg; Finn Bengtsson; Johan Ahlner; Aleksander A. Mathé; Linköpings universitet; []
   Nyckelord :;

   Sammanfattning : The blood-brain barrier (BBB) is formed by the capillary endothelial cells, joined together by tight junctions, with transporter proteins. BBB acts to regulate the brain concentrations of substances including many drugs. LÄS MER

3. 2. Clinical studies of CYP3A4 and P-glycoprotein

   Författare :Erik Sparve; Karolinska Institutet; Karolinska Institutet; []
   Nyckelord :;

   Sammanfattning : In the field of pharmacokinetics, cytochrome P450 enzymes have been extensively studied. The CYP450 enzyme with the most drug substrates is CYP3A4, but despite its significance, administration of a specific substrate to subjects is required to determine its activity, by measuring the metabolic ratio. LÄS MER

4. 3. ATP-Binding Cassette Efflux Transporters and Passive Membrane Permeability in Drug Absorption and Disposition

   Författare :Pär Matsson; Per Artursson; Ulf Norinder; Peter Swaan; Uppsala universitet; []
   Nyckelord :Pharmaceutics; ATP-binding cassette; ABC transporter; P-gp; P-glycoprotein; ABCB1; BCRP; Breast cancer resistance protein; ABCG2; MRP2; Multidrug-resistance associated protein 2; ABCC2; Membrane permeability; Drug transport; Active transport; Passive diffusion; Multivariate data analysis; PLS; OPLS; QSAR; Galenisk farmaci;

   Sammanfattning : Transport into and across the cells of the human body is a prerequisite for the pharmacological action of drugs. Passive membrane permeability and active transport mechanisms are major determinants of the intestinal absorption of drugs, as well as of the distribution to target tissues and the subsequent metabolism and excretion from the body. LÄS MER

5. 4. ATP-Binding-Cassette Transporters in Biliary Efflux and Drug-Induced Liver Injury

   Författare :Jenny M. Pedersen; Per Artursson; Christel A. S. Bergström; Stefan Oswald; Uppsala universitet; []
   Nyckelord :MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; ABC transport protein; Pgp; P-glycoprotein; ABCB1; BCRP; breast cancer resistance protein; ABCG2; MRP2; multidrug resistance-associated protein 2; ABCC2; BSEP; bile salt export pump; ABCB11; sandwich cultured human hepatocytes; SCHH; drug-induced liver injury; DILI; multivariate data analysis; OPLS; Galenisk farmaci; Pharmaceutics;

   Sammanfattning : Membrane transport proteins are known to influence the absorption, distribution, metabolism, excretion and toxicity (ADMET) of drugs. At the onset of this thesis work, only a few structure-activity models, in general describing P-glycoprotein (Pgp/ABCB1) interactions, were developed using small datasets with little structural diversity. LÄS MER

7. 5. Drug Transport and Metabolism in Rat and Human Intestine

   Författare :Sofia Berggren; Hans Lennernäs; Janet Hoogstraate; Patrick Augustijns; Uppsala universitet; []
   Nyckelord :Biopharmacy; Ussing chamber; microsome; single-pass perfusion; human; rat; intestine; permeability; efflux; P-glycoprotein; metabolism; cytochrome P450; ropivacaine; lidocaine; bupivacaine; Biofarmaci; PPX;

   Sammanfattning : One of the aims of this thesis was to investigate the involvement of efflux proteins, such as the P-glycoprotein (Pgp), in the drug transport in different regions of the rat and the human intestine. The intestinal extrusion of intracellularly formed CYP3A4 metabolites, including whether this extrusion might be mediated by Pgp, was also studied. LÄS MER