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Pharmacokinetic Modeling for In Vitro/In Vivo Transdermal Absorption


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dc.contributor.advisorRamapuram, Jayachandra Babu
dc.contributor.authorLee, Yann-Huei
dc.date.accessioned2017-11-29T17:06:29Z
dc.date.available2017-11-29T17:06:29Z
dc.date.issued2017-11-29
dc.identifier.urihttp://hdl.handle.net/10415/6016
dc.description.abstractThe objective was to determine if a linear pharmacokinetic model could be developed to describe in vitro and in vivo transdermal absorption across normal and microporated skin. Such a model would enable formulators to predict the effects of rate of drug delivery on pharmacokinetics and assist with dosage form design. An important concern for transdermal formulations is skin reactions, which can occur due to components of the transdermal product or from pre-existing skin conditions. The reactions can be reduced by the modification of the formulation or delivery method. Beta-blockers, such as propranolol, acebutolol, atenolol, and sotalol, are explored by transdermal passive diffusion, iontophoresis and microporation. Transdermal delivery offers the advantage of avoiding hepatic first pass metabolism. Though pharmacokinetic modeling of transdermal delivery is evident, such models have not been applied to microneedle and iontophoresis enhancement techniques. The pharmacokinetics of two aminoglycoside antibiotics in a topical cream were determined from a series of plasma drawn on day 1 and 20, shortly before application of the cream and in the minutes and hours immediately afterwards, as well as single samples periodically in between. The data set contained 573 observations, with greater than 1100 dosing events. Pharmacokinetic results were determined from traditional noncompartment analysis. Although the pharmacokinetics and safety of these antibiotics separately were well known, it had not been determined to what extent they would be absorbed into systemic circulation when applied to the open skin wounds of cutaneous leishmaniasis lesions. From the results, one aminoglycoside showed a wide range of variation, and many of the results were below the lower limit of quantification. No pharmacokinetic analysis was performed with the second aminoglycoside as most plasma concentrations were below the limits of detection. The sources and correlations of variability in drug concentrations among the target patient population can be used to determine population pharmacokinetics. Certain patient features, such as body weight, excretory and metabolic functions, and the presence of other therapies, can regularly alter dose-concentration relationships. The collection of relevant pharmacokinetic information in patients who are representative of the target population can help develop a quantitative estimation of the magnitude of the unexplained variability in the patient population. In addition, the skin permeation of various cobalamins across dermatomed and microporated human skin was studied to identify cobalamins that provide better skin absorption. Preliminary data for linear pharmacokinetic modeling was gathered to describe the in vitro absorption of four cobalamin derivatives: cyanocobalamin, hydroxocobalamin, methylcobalamin, and adenosylcobalamin. Correlation between in vitro absorption through microporated skin and the properties of the cobalamins was examined. No measureable levels of any of the B12 vitamins were detected in the passive diffusion experiments.en_US
dc.rightsEMBARGO_NOT_AUBURNen_US
dc.subjectInterdepartmental Pharmacyen_US
dc.titlePharmacokinetic Modeling for In Vitro/In Vivo Transdermal Absorptionen_US
dc.typePhD Dissertationen_US
dc.embargo.lengthMONTHS_WITHHELD:60en_US
dc.embargo.statusEMBARGOEDen_US
dc.embargo.enddate2022-11-28en_US
dc.contributor.committeeRavis, William
dc.contributor.committeeParsons, Daniel
dc.contributor.committeeArnold, Robert
dc.contributor.committeeJudd, Robert

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