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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Main Author:	Orwa, Albitar
Format:	Thesis
Language:	English
Published:	2022
Subjects:	RS1-441 Pharmacy and materia medica
Online Access:	http://eprints.usm.my/59662/1/24%20Pages%20from%20ALBITAR%20ORWA%20-%20TESIS.pdf
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id	my-usm-ep.59662
record_format	uketd_dc
spelling	my-usm-ep.596622023-12-13T01:21:21Z Pharmacokinetics And Pharmacodynamics Modeling Of Clozapine In Healthy Volunteers And Patients With Schizophrenia Spectrum Disorders Using Pharmacometrics Approach 2022-09 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 http://eprints.usm.my/59662/ http://eprints.usm.my/59662/1/24%20Pages%20from%20ALBITAR%20ORWA%20-%20TESIS.pdf application/pdf en public phd doctoral Perpustakaan Hamzah Sendut Pusat Pengajian Sains Farmasi
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	RS1-441 Pharmacy and materia medica
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
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.
format	Thesis
qualification_name	Doctor of Philosophy (PhD.)
qualification_level	Doctorate
author	Orwa, Albitar
author_facet	Orwa, Albitar
author_sort	Orwa, Albitar
title	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_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_sort	pharmacokinetics and pharmacodynamics modeling of clozapine in healthy volunteers and patients with schizophrenia spectrum disorders using pharmacometrics approach
granting_institution	Perpustakaan Hamzah Sendut
granting_department	Pusat Pengajian Sains Farmasi
publishDate	2022
url	http://eprints.usm.my/59662/1/24%20Pages%20from%20ALBITAR%20ORWA%20-%20TESIS.pdf
_version_	1794024029509648384

Pharmacokinetics And Pharmacodynamics Modeling Of Clozapine In Healthy Volunteers And Patients With Schizophrenia Spectrum Disorders Using Pharmacometrics Approach

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