The pharmacokinetics of phenytoin is complicated by the nonlinearity of the dose-concentration relationship which is a consequence of capacity-limited metabolism. Individualized therapy with phenytoin is therefore optimally required. As no data are available on the population pharmacokinetics of phenytoin in the Western Cape, this study was undertaken to address this issue. This study was conducted prospectively primarily to: (1) investigate the influence of various patient variables on the population pharmacokinetic parameters of phenytoin, (2) assess whether the parallel Michaelis-Menten and first-order elimination model provides a better fit to the data than the Michaelis-Menten model, (3) determine population pharmacokinetic parameter estimates of phenytoin representative of the patient population, and (4) validate and compare the clinical applicability of the parameter estimates and the models. The study population comprised 332 black and coloured, adult, male and female epileptic patients residing in the Western Cape, South Africa. All patients were on phenytoin monotherapy for the management of their epilepsy and no drugs known to interfere with phenytoin pharmacokinetics were taken concurrently. Clinical pharmacokinetic dosing services were initiated at 9 clinics from which patients were selected for this study. The service entailed a patient interview, a chart review, drug analysis and provision of either a written or verbal consultation report. The data were analyzed using NONMEM (nonlinear mixed-effects modelling), a computer programme designed for population pharmacokinetic analysis that allows pooling of data from many individuals. The Michaelis-Menten and the parallel Michaelis-Menten and first-order elimination models were fitted to 853 steady-state dose: serum concentration pairs.

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The aims of this research were to establish the drug use patterns of an elderly population in the southern suburbs of the Cape peninsula and to determine the extent of knowledge with respect to their medicines. In addition, the relationship between drug use patterns and medication knowledge and the socioeconomic status of the elderly, the health care services utilised by them and the amount of information conveyed on medicine container labels was assessed. Two hundred and sixty non-institutionalised Caucasian elderly over the age of 65 years and living in old age residences were interviewed. The interviews were structured with 4 major components: 1. a questionnaire designed to collect participant particulars; 2. an interview schedule to collect information on drug use patterns and to assess participant knowledge of medicines used (Knowledge score). 3. a container label assessment schedule (Label score); 4. a cognitive function test to identify and exclude severely cognitively impaired elderly from the study population. Analysis of the data showed the majority of the participants were English-speaking women of social class 1 or 2. Approximately one fifth of all participants were male. The State-run health care services were utilised by 38% of the participants whilst 73% retained their own general practitioner. A total of 843 medicines were used with an average of 3.2 medicines per capita. Ninety-five percent of all participants took prescribed medicines, with diuretics, non-narcotic analgesics/antipyretics, and tranquillisers the 3 most frequently prescribed classes. A smaller percentage - 41.5% - of participants used self-prescribed medicines, of which non-narcotic analgesics, homeopathic and herbal medicines, and vitamins were taken most frequently. When assessed against container label directions approximitely one third of participants were non-compliant with their dosage regimens. The majority of all medicines had been used on a continuous basis for 1 to 10 years. Average knowledge score was 58%. The majority of participants had very little knowledge about interactions, side effects, and maximum permissible dose for their medicines. Just over one fifth of all participants could correctly state both the name and the strength of their medicine. Average knowledge score was found to decline with increasing age, but no relationships were found to exist with the other patient characteristics. Similarly, no relationship was found to exist between knowledge score and label score. Participants utilising the public health care services tended to have a lower knowledge score than those receiving treatment from the private sector. Twenty-six percent of all labels did not have specific usage directions. The private sector suppliers were most frequently culpable of omitting instructions. Label legibility also proved to be a problem for the elderly participants. The drug use patterns identified in this study are similar to those of the American and British elderly and should be of value in compiling a health care plan for the South African elderly, although further research involving other race and cultural groups is needed.

This dissertation reports the findings of a study which was carried out in the Cape Town City Council area, in order to establish whether the offering of rifampicin to household contacts, of patients with meningococcal disease, resulted in protection of those contacts against developing the disease during a 32 week follow up period. The study took the form of a retrospective follow up of 3 350 household contacts of 412 cases notified over a 4-year period (mid 1988-mid 1992). It was found that the offering of rifampicin to the household contacts resulted in an odds ratio of not developing meningococcal disease over the 32-week follow up period of 14, 17 (SD = 12, 34). Although there was a tendency for contacts who were not offered rifampicin to have been younger, and of male gender, when compared to those who were offered prophylaxis, these demographic differences were not statistically significant at the 0,05 level. Furthermore, three out of the four male second cases, all in the younger age group, were in fact offered prophylaxis. It seems desirable that prophylaxis should be given as soon as possible. It is concluded, therefore, that the offering of rifampicin to household contacts of patients with meningococcal disease, living under the prevailing social circumstances in the Western Cape, has protective benefit for those contacts. It is likely that the chemoprophylaxis programme prevented up to 88 cases of meningococcal disease over the study period of four years, as well as preventing 8 deaths from this disease, in the CCC population.