The presence and seasonal variability of human and veterinary pharmaceuticals in surface water (raw water) and treated water samples from two drinking water facilities in Southern Ontario was investigated. Water samples were collected at monthly intervals for one year to characterize the seasonal variability of these contaminants. The presence of these compounds in raw water samples collected from groundwater wells, which were potentially under the influence of surface water, was also examined. All samples were extracted by solid phase extraction (SPE) techniques and analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-ESI-MS/MS). The compounds detected represented different therapeutic classes, including antibiotics, lipid regulating agents and anti-inflammatory drugs. The concentrations detected for most compounds were in the low ng/L range, with one compound being detected close to 1 μg/L. In general, human pharmaceuticals (i.e. gemfibrozil, ibuprofen and carbamazepine) were detected in raw and treated water samples, while the antibiotics were not detected after treatment. Seasonal variability was observed in the concentrations and compounds detected, which could be partially explained by changes in surface water hydrology and sources of contamination. The results demonstrate that the application of conventional treatment technologies were not very effective in reducing some of these compounds from a drinking water facility. In contrast, a second drinking water facility using additional treatment technologies, including ozonation and granular activated carbon (GAC) filters, could reduce the concentrations of these contaminants. Although, the presence of these contaminants in surface water represents a potential risk, the results suggest that appropriate treatment can minimize exposure to at least some of these emerging contaminants.

The presence and seasonal variability of human and veterinary pharmaceuticals in surface water (raw water) and treated water samples from two drinking water facilities in Southern Ontario was investigated. Water samples were collected at monthly intervals for one year to characterize the seasonal variability of these contaminants. The presence of these compounds in raw water samples collected from groundwater wells, which were potentially under the influence of surface water, was also examined. All samples were extracted by solid phase extraction (SPE) techniques and analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-ESI-MS/MS). The compounds detected represented different therapeutic classes, including antibiotics, lipid regulating agents and anti-inflammatory drugs. The concentrations detected for most compounds were in the low ng/L range, with one compound being detected close to 1 μg/L. In general, human pharmaceuticals (i.e. gemfibrozil, ibuprofen and carbamazepine) were detected in raw and treated water samples, while the antibiotics were not detected after treatment. Seasonal variability was observed in the concentrations and compounds detected, which could be partially explained by changes in surface water hydrology and sources of contamination. The results demonstrate that the application of conventional treatment technologies were not very effective in reducing some of these compounds from a drinking water facility. In contrast, a second drinking water facility using additional treatment technologies, including ozonation and granular activated carbon (GAC) filters, could reduce the concentrations of these contaminants. Although, the presence of these contaminants in surface water represents a potential risk, the results suggest that appropriate treatment can minimize exposure to at least some of these emerging contaminants.

The central objective of this study is to examine the factors that have influenced the evolution of the drug patenting regulatory framework in Canada from 1965 to 2005. The principal focus is on the extent to which in formulating that regulatory framework the Canadian federal government has been influenced by domestic and international interests and forces. In examining the domestic interests and forces attention is devoted to the financial interests of the two sectoral associations representing the patented and generic drug manufacturers and the economic and political interests of the governing and opposition parties. In examining the international interests and forces the focus is both on the emergence of international institutions and agreements and on the interests of various countries and drug companies located therein which wanted to ensure that Canadas regulatory framework would not have an adverse effect on them. This study reveals that there was three relatively distinct phases in the evolution of Canadas drug patenting regulatory framework and that each was influenced primarily by different sets of factors. The first phase which lasted from 1965 to 1991 was influenced entirely by domestic interests and forces produced by a highly charged political debate over reduced patent protection and drug price restrictions on the one hand, and increased patent protection and economic development on the other. The second phase, which lasted from 1992 to 2001, consisted largely of international forces. This included the emergence of new international institutions and agreements such as the World Trade Organization and the North American Free Trade Agreement, which created new intellectual property obligations for Canada and provided for even longer periods of patent protection than what had already existed. The third phase which began 2002 and continues to the present day, consists of a combination of domestic and international forces which attempt to reconcile domestic issues such as price restriction and economic development with international issues such as allowing Third World countries an opportunity to import drugs at reasonable prices. The Government of Canadas response to all of these pressures has predominantly reflected the objectives of patented drug manufacturers.

<p>My dissertation explores the interactions between the various agents in the pharmaceutical industry and how they are affected by changes in health care policy. In my work, I examine innovation and competition among new brand drugs and the value of prescription drug insurance after patent expiration.</p><p>The second chapter of my dissertation empirically assesses the trade-off between patent breadth and patent length, a topic that has attracted significant theoretical but little empirical attention. I estimate a model of pharmaceutical demand and supply that incorporates insurance and advertising for the antidepressant market. Using these estimates, I consider the potential welfare effects of giving some of the most important product innovations broader but shorter patents, which increases the market power that these innovators have in the short-run but also allows for more rapid entry by generics. My results indicate that in this setting broader patents could increase total welfare by more than 9%, mostly through savings in insurer expenditures. These results are robust to endogenizing the entry of other branded drugs.</p><p>In the third chapter, which stems from research done jointly with Peter Arcidiacono, Paul Ellickson, and David Ridley, I use data from the pharmaceutical industry to estimate demand and supply for prescription drugs across both insured and uninsured consumers, allowing for consumer preferences organized into discrete types. I account for an important characteristic of health care markets: the price paid by insured consumers (copayment) is typically much smaller than the price received by the manufacturer. This analysis highlights how generic-drug availability differentially affects insured and uninsured consumers. In particular, generic entry disproportionately benefits insured consumers, at least in the first year to two years.</p><p>The fourth chapter in my dissertation extends the analysis in Chapter 2 to allow for a more generalized framework. In Chapter 2, the first pharmaceutical product innovation that enters a therapeutic class is assumed to be high-value while those innovations that follow are assumed to provide relatively little, if any, added therapeutic value beyond the first. Using the same data and demand model estimates, I consider the potential welfare effects of allowing these later to be considered high-value products and providing them with greater patent breadth and shorter patent length. My results indicate that in this setting, the modified patent policy could still increase total welfare by more than 8%, mostly through savings in insurer expenditures. These results are also robust to endogenizing the entry of other branded products.</p> / Dissertation

Outsourcing of pharmaceutical manufacturing processes from developed countries to emerging economies such as India and China, has become increasingly frequent during the last decade. Simultaneously, impacts and risks associated with pharmaceuticals in the environment, particularly from manufacturing of Active Pharmaceutical Ingredients (APIs), have gained recognition as major threats to sustainable development, locally (due to pollution of ground- and surface water) as well as globally (due to risks with antibiotic resistance development). The purpose with this study is to examine the pollution situation in two main locations for API manufacturing in Andhra Pradesh, and its challenges, as well as the eventual possibilities and barriers to improve the situation. Based on semi-structured interviews with local stakeholders from industry, government and NGOs, site observations and community visits in affected areas, as well as a literature review, a critical examination of the situation and its potential sustainability measures was made. Furthermore, the connection to- and role of Swedish actors were explored. The study finds that there are major institutional challenges rather than technological ones, obstructing substantial improvements from taking place. Potential possibilities for pollution abatement include local initiatives e.g. alternative regulatory approaches as well as initiatives by international actors, such as large procurers of pharmaceuticals e.g. the Swedish county councils, which with policy instruments such as Green Public Procurement (GPP), pro-active and internationally coordinated efforts, could contribute to an improved situation.

Pharmaceuticals are environmental pollutants that are a major threat to aquatic ecosystems and very little is known about their ecological consequences. In this study growth, survival and behaviour (sociability, activity and boldness) of perch fry (Perca fluviatilis) were examined in order to study the possible effects of exposure to a benzodiazepine anxiolytic drug, Oxazepam, during embryonic development. The study tested following hypotheses: (1) perch growth is affected positively by exposure during embryonic development; (2) early perch survival is affected positively by exposure during embryonic development; and (3) boldness and activity increases while sociability decreases in perch fry exposed during embryonic development. Embryos of naturally spawned perch were exposed to water with two different concentrations of Oxazepam. The embryos were exposed during different parts (24-hour periods) of the embryonic development, because embryos may be more vulnerable at certain times during embryonic development and/or because the exposure at different times can produce different effects. Embryos were also chronically exposed, which is essential for aquatic systems because the influx of pharmaceuticals is more or less continuous. In line with hypothesis 1 treatment with Oxazepam affected growth positively. Similarly, survival increased with Oxazepam exposure as predicted by hypothesis 2. Perch fry exposed to the high concentration and fry exposed late during embryonic development survived better. In addition, as hypothesized in hypothesis 3, perch fry exposed to both concentrations exhibited increased activity and reduced sociability although boldness did not increase. Further studies are required to demonstrate the ecological consequences of Oxazepam in aquatic systems.

<div> This dissertation consists of three essays examining the nature of pricing in the pharmaceutical industry and the behavior of physicians prescribing drugs. I use a combination of structural modeling and reduced-form econometric techniques to illuminate how factors such as bargaining, competition, and network membership can affect prices and prescribing behavior. Ultimately, these insights can be used to influence public policy goals such as reducing prescription drug costs for patients or limiting unnecessary prescribing. </div><div> </div><div> In Chapter One, which is joint work with Sebastian Linde and Ralph Siebert, I focus on the determinants and effects of bargaining power on wholesale pharmaceutical drug prices. We estimate a structural bargaining model and find that large differences in bargaining power explain drug price heterogeneities across buyers, drug classes, and time periods. Our results show that transaction-specific determinants between buyers and sellers (such as transaction volume, buyer's loyalty, multiple drug purchases from the same seller, etc.) exert strong effects on buyer bargaining power and drug prices. Our counterfactuals show that group purchasing organizations achieve price reductions that vary across drug classes and that these price reductions primarily depend on buyer price sensitivity.</div><div> </div><div> In the second chapter, joint with G\"unter Hitsch, Sebastian Linde, and Ralph Siebert, I turn to the retail prescription drug market. Here, we show that there is a significant amount of price variation for prescription drugs in the retail pharmaceutical market. Both negotiated prices (price between retail pharmacies and third-party insurers) and out of pocket prices (prices between retail pharmacies and insured patients) for a drug exhibit a high degree of price variation even when controlling for drug manufacturer, geographic location, pharmacy chain, etc. Furthermore, the nature of this price variation changes depending on if a drug is branded or generic. </div><div> </div><div> In the third chapter, joint with Svetlana Beilfuss and Sebastian Linde, I examine the problem of antimicrobial resistance and how physician membership in Accountable Care Organizations (ACOs) can influence antibiotic prescribing behavior. We use a two-part structural model that accounts for selection into treatment (the ACO group), and non-treatment (control group). We then compare physician antibiotic prescribing across these groups with adjustment for volume, patient, physician, and institutional characteristics. We find that ACO affiliation reduces antibiotic prescribing by about 23\% per year. Furthermore, we show that failure to account for selection into treatment results in an understating of the average treatment effect.</div>

The advancement of medicine around the world is happening at a rapid speed. There is not a day that one does not hear about a disease being cured or a wonder-drug being developed. Medicine has always been a field that treated a sick patient to bring that person back to “normal” function, which could be said to be the state he or she was in before acquiring the disease in question. However, due to scientific breakthroughs humanity is in a position that historically it has never been before. A place where a person can increase their mental and physical performance using pharmaceuticals to a level where genetics and upbringing alone would not have allowed. Pharmaceuticals have been created which can do for the brain what has been done for the body. These drugs provide an avenue in which a person’s cognitive functions can be increased beyond what was otherwise possible. The ethical and legal dilemmas posed by prescribing or allowing people to use nootropics is hotly debated. Greely, a leading figure in the bioethical debate, in connection with nootropics, has stated that the ethical concerns comprise three main aspects: safety, fairness and coercion., It is clear that these three aspects cover a wide ambit. The arguments for and against nootropics will not merely be rehashed but rather placed into the South African context to ascertain how best to provide for the ethical concerns relevant to South Africa. The ethics of nootropic use will be examined through the lens of the Beuchamp Childress model which determines ethical problems using the principles of autonomy, justice, beneficence and non-maleficence. The aim and contribution of this thesis will be to build a legal framework for the use of nootropics in South Africa, to create this one must ascertain what the current legal position is. Law is built from precedent in context of case law and legislation. The current law will be examined to see what can be used, what may need to be discarded and what would need to be added. A layered approach is used to determine what the legal position in South Africa currently is. A layered approach looks at the constitution and proceeds to legislation, case law, and legal articles and books. A major aspect around the use of nootropics will be informed consent and how it relates to the use of nootropics especially with regards to adolescents i.e. under 18 years of age. This thesis follows an MPhil in Medical Law and Ethics which outlined the doctrine of informed consent in South Africa and thus allows for the application of this doctrine to a pressing issue in South African society. / Thesis (PhD)--University of Pretoria, 2019. / Public Law / PhD / Unrestricted

Effects of solubility, partition coefficient, pH and selected adjuvants (propylene glycol and Azone) on the percutaneous penetration of isoproterenol HC1 in vitro have been investigated using human cadaver skin. Preliminary stability studies demonstrated that isoproterenol HC1 was very stable (less than 1% decomposition) for 24 hours at 22(DEGREES) (+OR-) 0.5(DEGREES) in the pH range 1 to 7 in the following solvents: water, normal saline, propylene glycol and a series of propylene glycol-water mixtures (10,20,40 and 60% v/v). The rate of decomposition of the drug in aqueous solutions increased with pH beyond pH 8. In normal saline, the decomposition was significant when the temperature was raised to 37(DEGREES) (+OR-) 0.5(DEGREES). The solubility of isoproterenol HC1 decreased and its skin/vehicle partition coefficient increased with increasing proportions of propylene glycol in the vehicle. Results of the physicochemical and percutaneous penetration studies revealed that 20% v/v propylene glycol in water should be the optimal vehicle for transdermal delivery of isoproterenol HC1. Optimal penetration enhancing effects of AzoneR were seen when incorporated at a concentration of 1% v/v in the 20% v/v propylene glycol-water vehicle and more dramatically when the skin was pretreated with pure Azone for 60 minutes prior to application of the drug formulation. The flux reached a maximum around pH 9 in agreement with the predicted favorable pH environment for neutral forms of isoproterenol HC1. Both neutral and charged forms of isoproterenol HC1 were found to contribute to the total flux in agreement with the proposed model: J = ( Kp . C )ca + ( Kp . C )an + ( Kp . C )n. The calculated permeability coefficients for isoproterenol HC1 were 0.2098 x 10-3, 0.1570 x 10-4 and -0.8665 x 10-3 cm/h for neutral, cationic and anionic species, respectively. Azone enhanced the penetration of all forms of isoproterenol HC1, although the effect was more pronounced on the anionic species. This may be due to facilitation of penetration by formation of an ion-pair between isoproterenol HC1 and Azone. The permeability coefficients for the neutral, cationic and anionic forms of isoproterenol HC1 for penetration through Azone-pretreated skin were 0.8395 x 10-3, 0.1701 x 10-3 and 0.8091 x 10-2 cm/h, respectively.

No description available.