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Age-Associated Expression Patterns Of Oatp 1b1 And Oatp 1b3 And Their Effect On The Disposition Of Fexofenadine, Margaret Mary Thomson

Theses and Dissertations (ETD)

As part of the drug disposition process (absorption, distribution, metabolism, excretion), an often overlooked aspect is transport. In order for drugs to be metabolized and excreted from the body they go through the liver or other drug removal organs. For drugs that are polar or are large they must rely upon transport mechanisms to transport them across the biomembranes of the drug removal organs. OATP1B1 and OATP1B3 are transporters on the sinusoidal membrane of the liver which work in concert with the drug metabolizing enzymes as part of the drug removal process. It is known that the development of each …

Challenges In The Pharmacokinetics Of Therapeutic Proteins, Wararat Limothai

Theses and Dissertations (ETD)

Due to the complex structure and complicated disposition pattern of therapeutic macromolecules, their pharmacokinetic interpretation has many challenges. Two of these challenges were investigated in this dissertation: 1) the error of classical bioavailability assessment observed during subcutaneous (SC) administration of therapeutic macromolecules that undergo target-mediated drug disposition (TMDD) and 2) the ontogeny of the neonatal Fc receptor (FcRn) expression along with its effect on the pharmacokinetics of monoclonal antibodies (mAbs) during development.

TMDD often well describes the pharmacokinetics of therapeutic proteins that have high specificity and affinity of binding to their target receptors. The target receptors can be saturated by …

Age-Associated Hepatic Drug Transporter Expression And Its Implications For Pediatric Pharmacotherapyflexibility Affect Dna Topoisomerase I Function, Lisa Tang

Theses and Dissertations (ETD)

Members of the ATP-binding cassette (ABC) family of drug transporter proteins translocate various endogenous and exogenous substrates across intra- and extracellular membranes. Two specific ABC transporters, the multidrug resistance 1/P-glycoprotein (MDR1/P-gp) and the multidrug resistance protein 2 (MRP2), serve as major hepatic transporters that mediate the biliary excretion of various organic anions and cations along with glutathione-, glucuronate-, or sulfate-conjugates of several drug substrates. However, very little is known about the expression of these transporters in the early infant and childhood ages of human development. We, therefore, characterized the ontogeny of these transporters by measuring their gene and protein expression. …