Pharmacokinetics And Pharmacodynamics Modeling Of Clozapine In Healthy Volunteers And Patients With Schizophrenia Spectrum Disorders Using Pharmacometrics Approach
Clozapine is the first-line medication for treatment-resistant schizophrenia. However, it has complex metabolism, an unclear exposure-response relationship, and potential adverse drug reactions (ADRs). The present study aimed to develop an analytical method and pharmacometrics-based models for cloza...
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| Format: | Thesis |
| Language: | English |
| Published: |
2022
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| Online Access: | http://eprints.usm.my/59662/1/24%20Pages%20from%20ALBITAR%20ORWA%20-%20TESIS.pdf |
| _version_ | 1825908130527051776 |
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| author | Orwa, Albitar |
| author_facet | Orwa, Albitar |
| author_sort | Orwa, Albitar |
| collection | USM |
| description | Clozapine is the first-line medication for treatment-resistant schizophrenia. However, it has complex metabolism, an unclear exposure-response relationship, and potential adverse drug reactions (ADRs). The present study aimed to develop an analytical method and pharmacometrics-based models for clozapine and norclozapine pharmacokinetics and pharmacodynamics in healthy volunteers and schizophrenia spectrum disorder (SSD) patients. A surfactant-assisted dispersive liquid-liquid microextraction coupled with HPLC-UV was used for clozapine and norclozapine determination after optimizing experimental factors. 270 data points obtained from 33 healthy volunteers after receiving a single dose of 12.5 mg clozapine were utilized in the semi-physiological pharmacokinetic model development incorporating the pre-systemic clozapine metabolism. To assess clozapine interaction with pantoprazole, a randomized, crossover, open-label study design was implemented. 12 volunteers were given clozapine alone; then clozapine after five days of 40 mg pantoprazole or vice versa, separated by a washout period. Meanwhile, clinical data were extracted from 116 SSD patients’ medical records in Penang General Hospital, with a mean retrospective follow-up of 306 weeks. |
| first_indexed | 2024-03-06T16:14:24Z |
| format | Thesis |
| id | usm.eprints-59662 |
| institution | Universiti Sains Malaysia |
| language | English |
| last_indexed | 2024-03-06T16:14:24Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | usm.eprints-596622023-12-13T01:21:21Z http://eprints.usm.my/59662/ Pharmacokinetics And Pharmacodynamics Modeling Of Clozapine In Healthy Volunteers And Patients With Schizophrenia Spectrum Disorders Using Pharmacometrics Approach Orwa, Albitar RS1-441 Pharmacy and materia medica Clozapine is the first-line medication for treatment-resistant schizophrenia. However, it has complex metabolism, an unclear exposure-response relationship, and potential adverse drug reactions (ADRs). The present study aimed to develop an analytical method and pharmacometrics-based models for clozapine and norclozapine pharmacokinetics and pharmacodynamics in healthy volunteers and schizophrenia spectrum disorder (SSD) patients. A surfactant-assisted dispersive liquid-liquid microextraction coupled with HPLC-UV was used for clozapine and norclozapine determination after optimizing experimental factors. 270 data points obtained from 33 healthy volunteers after receiving a single dose of 12.5 mg clozapine were utilized in the semi-physiological pharmacokinetic model development incorporating the pre-systemic clozapine metabolism. To assess clozapine interaction with pantoprazole, a randomized, crossover, open-label study design was implemented. 12 volunteers were given clozapine alone; then clozapine after five days of 40 mg pantoprazole or vice versa, separated by a washout period. Meanwhile, clinical data were extracted from 116 SSD patients’ medical records in Penang General Hospital, with a mean retrospective follow-up of 306 weeks. 2022-09 Thesis NonPeerReviewed application/pdf en http://eprints.usm.my/59662/1/24%20Pages%20from%20ALBITAR%20ORWA%20-%20TESIS.pdf Orwa, Albitar (2022) Pharmacokinetics And Pharmacodynamics Modeling Of Clozapine In Healthy Volunteers And Patients With Schizophrenia Spectrum Disorders Using Pharmacometrics Approach. PhD thesis, Perpustakaan Hamzah Sendut. |
| spellingShingle | RS1-441 Pharmacy and materia medica Orwa, Albitar Pharmacokinetics And Pharmacodynamics Modeling Of Clozapine In Healthy Volunteers And Patients With Schizophrenia Spectrum Disorders Using Pharmacometrics Approach |
| title | Pharmacokinetics And Pharmacodynamics Modeling Of Clozapine In Healthy Volunteers And Patients With Schizophrenia Spectrum Disorders Using Pharmacometrics Approach |
| title_full | Pharmacokinetics And Pharmacodynamics Modeling Of Clozapine In Healthy Volunteers And Patients With Schizophrenia Spectrum Disorders Using Pharmacometrics Approach |
| title_fullStr | Pharmacokinetics And Pharmacodynamics Modeling Of Clozapine In Healthy Volunteers And Patients With Schizophrenia Spectrum Disorders Using Pharmacometrics Approach |
| title_full_unstemmed | Pharmacokinetics And Pharmacodynamics Modeling Of Clozapine In Healthy Volunteers And Patients With Schizophrenia Spectrum Disorders Using Pharmacometrics Approach |
| title_short | Pharmacokinetics And Pharmacodynamics Modeling Of Clozapine In Healthy Volunteers And Patients With Schizophrenia Spectrum Disorders Using Pharmacometrics Approach |
| title_sort | pharmacokinetics and pharmacodynamics modeling of clozapine in healthy volunteers and patients with schizophrenia spectrum disorders using pharmacometrics approach |
| topic | RS1-441 Pharmacy and materia medica |
| url | http://eprints.usm.my/59662/1/24%20Pages%20from%20ALBITAR%20ORWA%20-%20TESIS.pdf |
| work_keys_str_mv | AT orwaalbitar pharmacokineticsandpharmacodynamicsmodelingofclozapineinhealthyvolunteersandpatientswithschizophreniaspectrumdisordersusingpharmacometricsapproach |