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The determination and validation of population pharmacokinetic parameters of phenytoin in adult epileptic patients in the Western Cape using nonlinear mixed-effects modelling
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 phe...
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| Format: | Thesis |
| Language: | English |
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Division of Clinical Pharmacology
2017
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| _version_ | 1867613215156862976 |
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| access_status_str | Open Access |
| author | Valodia, Praneet |
| author2 | Folb, Peter I |
| author_browse | Folb, Peter I Valodia, Praneet |
| author_facet | Folb, Peter I Valodia, Praneet |
| author_sort | Valodia, Praneet |
| collection | Thesis |
| description | 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. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/26609 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:32:36.207Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2017 |
| publishDateRange | 2017 |
| publishDateSort | 2017 |
| publisher | Division of Clinical Pharmacology |
| publisherStr | Division of Clinical Pharmacology |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/26609 The determination and validation of population pharmacokinetic parameters of phenytoin in adult epileptic patients in the Western Cape using nonlinear mixed-effects modelling Valodia, Praneet Folb, Peter I Seymour, M A Epilepsy - drug therapy - South Africa Phenytoin - pharmacokinetics 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. 2017-12-13T14:18:46Z 2017-12-13T14:18:46Z 1995 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/26609 eng application/pdf Division of Clinical Pharmacology Faculty of Health Sciences University of Cape Town |
| spellingShingle | Epilepsy - drug therapy - South Africa Phenytoin - pharmacokinetics Valodia, Praneet The determination and validation of population pharmacokinetic parameters of phenytoin in adult epileptic patients in the Western Cape using nonlinear mixed-effects modelling |
| thesis_degree_str | Doctoral |
| title | The determination and validation of population pharmacokinetic parameters of phenytoin in adult epileptic patients in the Western Cape using nonlinear mixed-effects modelling |
| title_full | The determination and validation of population pharmacokinetic parameters of phenytoin in adult epileptic patients in the Western Cape using nonlinear mixed-effects modelling |
| title_fullStr | The determination and validation of population pharmacokinetic parameters of phenytoin in adult epileptic patients in the Western Cape using nonlinear mixed-effects modelling |
| title_full_unstemmed | The determination and validation of population pharmacokinetic parameters of phenytoin in adult epileptic patients in the Western Cape using nonlinear mixed-effects modelling |
| title_short | The determination and validation of population pharmacokinetic parameters of phenytoin in adult epileptic patients in the Western Cape using nonlinear mixed-effects modelling |
| title_sort | determination and validation of population pharmacokinetic parameters of phenytoin in adult epileptic patients in the western cape using nonlinear mixed effects modelling |
| topic | Epilepsy - drug therapy - South Africa Phenytoin - pharmacokinetics |
| url | http://hdl.handle.net/11427/26609 |
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