Kritiskt sjuka patienter med infektioner är en börda för sjukvården och 70 % av alla patienter på intensivvårdsavdelningar är ordinerade antibiotika. Antibiotika binder till proteiner i blodet, men enbart den icke-proteinbundna (fria) fraktionen kan diffundera över kapillära membran och binda till receptorer. Standardproteinbindningsgrad för olika antibiotika har utvecklats från studier på friska frivilliga och doseringen av läkemedlen är anpassade därefter. Den totala koncentrationen av antibiotika i patienters blod är vanligen representativ för den farmakologiska effekten. Dock kan vissa sjukdomar påverka proteinbindningsgraden vilket resulterar i en större eller mindre mängd fria antibiotika i blodcirkulationen. Det här kan i sin tur resultera i toxicitet eller otillräcklig effekt av läkemedlet. Syftet med det här projektet var att utveckla en analytisk metod för att bestämma den fria koncentrationen av Beta-Lactam antibiotikan cefotaxim, flukloxacillin, kloxacillin och piperacillin i plasma. En metod utvecklades med ultrafiltrering för extraktion av den fria fraktionen och högupplösande vätskekromatografi och tandem masspektrometri, UHPLC-MS/MS, för kvantifiering av analyterna. Metoden validerades delvis enligt den Europeiska Läkemedelsmyndighetens riktlinjer för bioanalytisk metodvalidering. / Infections in critically ill patients are a problem for the healthcare system and at any one time, 70 % of all intensive care unit (ICU) patients are treated with antibiotics. Antibiotics bind to proteins in the blood, but only unbound drug can diffuse over capillary membranes and bind to the targeted receptor. Standard protein binding percentages for antibiotics have been developed from studies on healthy volunteers and dosing regimens for patients are adapted accordingly. The determination of the total concentration of antibiotics in patients’ blood samples is, based on the standard percentages, ordinarily representative for the pharmacological effect of the antibiotic. However, certain conditions that are common in critically ill patients can alter protein binding percentages, resulting in a larger or smaller unbound fraction. This in turn can result in toxicity or therapeutic failure. The aim of this project was to develop an analytical method for the determination of the unbound concentration of the Beta-Lactam antibiotics cefotaxime, flucloxacillin, cloxacillin and piperacillin in plasma. A method was successfully developed using ultrafiltration for the extraction of unbound analytes and ultra high performance liquid chromatography tandem mass spectrometry, UHPLC-MS/MS, for their quantification. The method was partly validated according to the European Medicines Agency’s guidelines on bioanalytical method validation.

The most frequent intervention performed by physicians is the writing of a prescription. Modern medicine has been remarkably effective in managing diseases. Medicines play a fundamental role in the effectiveness, efficiency and responsiveness of health care systems. However, health care expenditure is a great cause for concern and many nations around the world struggle to contain rising health care costs. Pharmaceutical benefit management programmes such as pharmacoeconomics, drug utilisation review (DUR) and disease management have emerged as control tools to ensure cost effective selection and use of medicine. These managed care instruments are often used to determine whether new strategies or interventions, such as the implementation of a managed medicine reference price list, are appropriate and have "value". The general objective of this study was to investigate the influences of the implementation of a managed medicine reference price list on the usage and cost of antibiotic medicine in the private health care sector of South Africa. The research design used in this study was retrospective, non-experimental and quantitative. The data used for the analysis were obtained over a two-year study period (1 May 2001 to 31 April 2003) from the central medicine claims database of Medschem&. Data was analysed according to prevalence, cost and original (innovator) or generic medicine items. For the purpose of this study antibiotics referred to beta-lactams (penicillins, cephalosporins and "others"), erythromycin and other macrolides, tetracyclines, sulphonamides and combinations, quinolones, chloramphenicol and aminoglycosides. The results of the empirical investigation showed the total number of medicine items claimed during the study period amounted to 49098736 medicine items having a total expenditure of R7150344897.00. There was a decrease in the prevalence of original (innovator) products during the two-year period. The prevalence of generic products increased from 25.87% to 32.47%. A total of 4092495 antibiotic medicine items were claimed with a total cost of R526309279.43 representing 7.36% (n = R7150344897.00) of all pharmaceutical products purchased during the two-year period. Original antibiotics had a prevalence of 42.32%, while generic antibiotics constituted 57.68% of all antibiotic products claimed (n = 4092495). However, original (innovator) products contributed 62.32% and generic products 37.68% to the total cost of all antibiotics claimed. It was concluded that the beta-lactam antibiotics represented 56.99% of all antibiotics claimed (n = 4092495) and contributed 52.51% to the total antibiotic expenditure (n = R526309279.43) for the two-year period. The average cost of beta-lactam items ranged between R112.88 * 69.95 and R122.18 + 81.42. The Medschema Price List (MPL) was implemented in May 2001. The aim of this reference pricing system was to allocate a ceiling price to a group of drugs, which are similar in terms of composition, clinical efficacy, safety and quality, with the ultimate goal to reduce medicine expenditure. During the year of implementation of the MPL 62.24% of beta-lactam antibiotics claimed (n = 1303464) were MPL listed. These products contributed 43.25% to the total cost of all beta-lactam antibiotics (n = R157142778.38). Medical aid companies reimbursed R61649211.86 for penicillins claimed and MPL listed. If all penicillin products were claimed at the ceiling price set by the MPL, a cost saving of 2.79% could have been achieved. Cost analysis indicated that it is possible to reduce health care costs by implementing strategies with the aim to reduce medicine cost. Further research, however, is necessary and in this regard recommendations for further research were formulated. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2005.

The most frequent intervention performed by physicians is the writing of a prescription. Modern medicine has been remarkably effective in managing diseases. Medicines play a fundamental role in the effectiveness, efficiency and responsiveness of health care systems. However, health care expenditure is a great cause for concern and many nations around the world struggle to contain rising health care costs. Pharmaceutical benefit management programmes such as pharmacoeconomics, drug utilisation review (DUR) and disease management have emerged as control tools to ensure cost effective selection and use of medicine. These managed care instruments are often used to determine whether new strategies or interventions, such as the implementation of a managed medicine reference price list, are appropriate and have "value". The general objective of this study was to investigate the influences of the implementation of a managed medicine reference price list on the usage and cost of antibiotic medicine in the private health care sector of South Africa. The research design used in this study was retrospective, non-experimental and quantitative. The data used for the analysis were obtained over a two-year study period (1 May 2001 to 31 April 2003) from the central medicine claims database of Medschem&. Data was analysed according to prevalence, cost and original (innovator) or generic medicine items. For the purpose of this study antibiotics referred to beta-lactams (penicillins, cephalosporins and "others"), erythromycin and other macrolides, tetracyclines, sulphonamides and combinations, quinolones, chloramphenicol and aminoglycosides. The results of the empirical investigation showed the total number of medicine items claimed during the study period amounted to 49098736 medicine items having a total expenditure of R7150344897.00. There was a decrease in the prevalence of original (innovator) products during the two-year period. The prevalence of generic products increased from 25.87% to 32.47%. A total of 4092495 antibiotic medicine items were claimed with a total cost of R526309279.43 representing 7.36% (n = R7150344897.00) of all pharmaceutical products purchased during the two-year period. Original antibiotics had a prevalence of 42.32%, while generic antibiotics constituted 57.68% of all antibiotic products claimed (n = 4092495). However, original (innovator) products contributed 62.32% and generic products 37.68% to the total cost of all antibiotics claimed. It was concluded that the beta-lactam antibiotics represented 56.99% of all antibiotics claimed (n = 4092495) and contributed 52.51% to the total antibiotic expenditure (n = R526309279.43) for the two-year period. The average cost of beta-lactam items ranged between R112.88 * 69.95 and R122.18 + 81.42. The Medschema Price List (MPL) was implemented in May 2001. The aim of this reference pricing system was to allocate a ceiling price to a group of drugs, which are similar in terms of composition, clinical efficacy, safety and quality, with the ultimate goal to reduce medicine expenditure. During the year of implementation of the MPL 62.24% of beta-lactam antibiotics claimed (n = 1303464) were MPL listed. These products contributed 43.25% to the total cost of all beta-lactam antibiotics (n = R157142778.38). Medical aid companies reimbursed R61649211.86 for penicillins claimed and MPL listed. If all penicillin products were claimed at the ceiling price set by the MPL, a cost saving of 2.79% could have been achieved. Cost analysis indicated that it is possible to reduce health care costs by implementing strategies with the aim to reduce medicine cost. Further research, however, is necessary and in this regard recommendations for further research were formulated. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2005.