Availability of pharmacoeconomic data and its use in the development of drug formularies in South Africa
- Authors: Keele, Mothobi Godfrey
- Date: 2008
- Subjects: Drugs -- Cost effectiveness , Pharmacy -- Economic aspects
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:10146 , http://hdl.handle.net/10948/685 , Drugs -- Cost effectiveness , Pharmacy -- Economic aspects
- Description: In an attempt to manage scarce health care resources and keep drug expenditure low, health care administrators worldwide have to make careful considerations regarding the choice of drugs to be provided to patients within their systems. One of the key strategies that is being employed to achieve this goal is the use of formularies. A major challenge in the formulary development process is to use pharmacoeconomics and outcomes research effectively to arrive at formularies that simultaneously provide patients with effective pharmacotherapy whilst maintaining financial stability. The extent to which this can be successfully achieved depends to a large extent on the availability of appropriate pharmacoeconomic data. The primary objectives of this study were to describe the availability and quality of literature pertaining to South African based pharmacoeconomic research, and to establish the manner in and extent to which pharmacoeconomic data is used in drug formulary decision-making processes, in both the private and public health care sectors in South Africa. A structured bibliographic search for South African pharmacoeconomic studies was conducted and a qualitative assessment of the identified studies which met the predetermined inclusion criteria was completed, using a pre-validated quality evaluation tool. In order to determine the use of pharmacoeconomic data in the formulary decisionmaking processes, by various stake holders in both the public and private of health care sectors in South Africa, a cross-sectional, descriptive study using a self-administered questionnaire was conducted. The results suggest that there is a limited availability of pharmacoeconomic research data in South Africa. Only 16 full pharmacoeconomic studies could be identified as having been published between 01 January 1995 and 30 June 2007. The quality of 3 of these studies was considered to be ‘dubious’, one study was found to be of high standard whilst the other 12 (74.95%) were of acceptable quality and thus could be considered as suitable to be used in formulary decision-making. The results of the national survey indicated that pharmacoeconomics is considered to be of importance and is used in formulary decision-making processes in both the public and private sectors. The primary source of pharmacoeconomic data used in formulary decisions appears to be international peer-reviewed publications. Of concern however, is the finding that this data, mostly from studies conducted outside of South Africa, is applied directly without sensitivity analysis or modelling. The results of the literature search and the subsequent quality appraisal suggest that pharmacoeconomic research and the use of pharmacoeconomic data in formulary decisions is at its infancy in South Africa. Thus efforts are needed to develop and grow the discipline of pharmacoeconomics in South Africa.
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- Date Issued: 2008
Evaluation of the pharmaceutical availability of erythromycin from topical formulations
- Authors: Mandimika, Nyaradzo
- Date: 2008
- Subjects: Pharmacy -- Research Chromatographic analysis Gel permeation chromatography Gels (Pharmacy) Chemistry, analytic Acne -- Treatment Sebaceous glands -- Diseases -- Treatment Drugs -- Testing Erythromycin -- Bioavailability
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3771 , http://hdl.handle.net/10962/d1003249
- Description: Erythromycin (ERY) is a macrolide antibiotic which is used in the treatment of acne vulgaris.Acne is a common skin condition that occurs when the sebaceous glands and hair shafts become infected by the bacteria Propionibacterium acnes. Acne is a chronic condition that may last for years and the severity of the effects of the disease on patients is often undermined especially in third world countries where more emphasis is placed on other more life-threatening diseases. It may cause considerable physical and emotional distress to sufferers along with the possibility of permanent scarring. Although use of topical ERY formulations is not the first line of treatment it has proven to be effective in treating inflammation of skin and skin structures cause by the responsible bacteria. To-date there are a variety of vehicles which are used in preparing topical ERY formulations namely ointment and gel bases, alcoholic solutions and pledgets. All the gel formulations on the market contain hydroxypropyl cellulose, alcohol and water along with the active ingredient(s). However, some gel formulations contain propylene glycol in addition to these excipients an example being Emgel®. Propylene glycol has been shown to affect the penetration of topically applied drugs through the skin suggesting that it would be highly likely that those formulations which contain propylene glycol may release more ERY into the skin following application. With this in mind, two ERY gel formulations were produced which contained different percentages of propylene glycol. According to the FDA guidelines, pharmacokinetic measurements in blood, plasma and/or urine of topical dermatological drug products are not feasible to document bioequivalence since the active ingredient(s) in topical formulations is/are not intended to be absorbed into the systemic circulation and in addition, concentrations in extracutaneous biological tissues would generally not be measurable. This limits determination of bioavailability and assessment of bioequivalence of such products to pharmacodynamic measurements, clinical trials and dermatopharmacokinetic (DPK) measurements such as tape stripping (TS) and microdialysis (MD).TS is a sampling technique which involves sequential removal of layers of the stratum corneum using strips of adhesive tape. This technique has found increasing use in DPK studies for investigation of drug kinetics in the skin following the application of a topical formulation. The technique has also been used as a diagnostic tool in assessing the quality of the stratum corneum in diseased skin. In the current research study, the tape stripping technique was used to investigate the pharmaceutical/biological availability of topical gel formulations containing ERY. MD is another DPK sampling technique which has been used to determine the amount of a topically applied drug that penetrates through the stratum corneum to reach deeper tissues of the skin. The in vivo sampling technique involves the insertion of microdialysis probes beneath the skin surface in the dermal tissue and allows for real-time sampling of the analyte at its target site. Recently in vitro MD has also been successfully used to assess the pharmaceutical availability of a topical corticosteroid, mometesone furoate, from topical formulations. Based on this work, microdialysis was used to determine the pharmaceutical availability of ERY from gel formulations which were developed for use in this research. The results of the pharmaceutical availability of ERY from in vivo tape stripping studies and the in vitro microdialysis studies were compared to establish correlation between the data. Pharmaceutical equivalence and bioequivalence data obtained from the respective studies on the gel formulations were investigated by statistical analysis of the data generated from both the in vitro and in vivo experiments. In summary the objectives of this research were: 1. To develop and validate a high performance liquid chromatography method suitable to analyse ERY concentrations obtained from in vitro microdialysis studies and in vivo tape stripping studies. 2. To prepare two different ERY gel formulations with different percentage content of propylene glycol. 3. To determine the pharmaceutical availability of ERY from two different gel formulations using in vitro microdialysis. 4. To develop and validate a tape stripping technique which could be used to determine percutaneous penetration and bioequivalence of the gel formulations. 5. To compare in vitro microdialysis and in vivo tape stripping data and attempt to establish a correlation between the two different approaches.
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- Date Issued: 2008
Neuroprotective mechanisms of nevirapine and efavirenz in a model of neurodegeneration
- Authors: Zheve, Georgina Teurai
- Date: 2008
- Subjects: HIV infections -- Treatment AIDS (Disease) -- Treatment AIDS dementia complex -- Treatment Nervous system -- Degeneration -- Treatment Melatonin Neurotoxic agents Quinolinic acid
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3807 , http://hdl.handle.net/10962/d1003285
- Description: AIDS Dementia Complex (ADC) is a neurodegenerative disorder implicated in HIV-1 infection that is associated with elevated levels of the neurotoxin, quinolinic acid (QA) which causes a cascade of events to occur, leading to the production of reactive oxygen species (ROS), these being ultimately responsible for oxidative neurotoxicity. In clinical studies, Non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz (EFV) and nevirapine (NVP) have been shown to potentially delay the progressive degeneration of neurons, thus reducing the frequency and neurological deficits associated with ADC. Despite these neuroprotective implications, there is still no biochemical data to demonstrate the mechanisms through which these agents offer neuroprotection. The present study aims to elucidate and further characterize the possible antioxidant and neuroprotective mechanisms of NVP and EFV in vitro and in vivo, using QA-induced neurotoxicity as a model. Research has demonstrated that antioxidants and metal chelators have the ability to offer neuroprotection against free radical induced injury and may be beneficial in the prevention or treatment of neurodegeneration. Hence the antioxidant and metal binding properties of these agents were investigated respectively. Inorganic studies, including the 1, 1-diphenyl-2 picrylhydrazyl (DPPH) assay, show that these agents readily scavenge free radicals in vitro, thus postulating the antioxidant property of these agents. The enhancement of superoxide radical generation and iron mediated Fenton reaction by QA is related to lipid peroxidation in biological systems, the extent of which was assayed using the nitroblue tetrazolium and thiobarbituric acid method respectively. Both agents significantly curtail QA-induced lipid peroxidation and potentially scavenge superoxide anions generated by cyanide in vitro. Furthermore, in vivo results demonstrate the ability of NVP and EFV to protect hippocampal neurons against lipid peroxidation induced by QA and superoxide radicals generated as a consequence thereof. The alleviation of QA-induced oxidative stress in vitro possibly occurs through the binding of iron (II) and / or iron (III), and this argument is further strengthened by the ability of EFV and not NVP to reduce iron (II)-induced lipid peroxidation in vitro directly. In addition the ferrozine and electrochemistry assay were used to measure the extent of iron (II) Fe[superscript 2+] and iron (III) Fe[superscript 3+] chelation activity. Both assays demonstrate that these agents bind iron (II) and iron (III), and prevent redox recycling of iron and subsequent complexation of Fe[superscript 2+] with QA which enhances neuronal damage. Both NNRTIs inhibit the endogenous biosynthesis of QA by inhibiting liver tryptophan 2, 3-dioxygenase activity in vivo and subsequently increasing hippocampal serotonin levels. Furthermore, these agents reduce the turnover of hippocampal serotonin to 5-hydroxyindole acetic acid. NVP and not EFV increase 5-hydroxyindole acetic acid and norepinephrine levels in the hippocampus. The results of the pineal indole metabolism study show that NVP increases the synthesis of melatonin, but decreases N-acetylserotonin, 5-hydroxyindole acetic acid and 5-hydroxytryptophol levels. Furthermore, it shows that EFV decreases 5-hydroxyindole acetic acid and melatonin synthesis. Behavioural studies using a Morris water maze show that the post-treatment of rats with NVP and EFV significantly improves QA-induced spatial memory deficits in the hippocampus. This study therefore provides novel information regarding the neuroprotective mechanisms of NVP and EFV. These findings strengthen the argument that these NNRTIs not only have antiviral effects but possess potential neuroprotective properties, which may contribute to the effectiveness of these drugs in the treatment of ADC.
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- Date Issued: 2008