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Changing the Drug Delivery System: Does it Add to Non-Compliance Ramifications Control? A Simulation Study on the Pharmacokinetics and Pharmacodynamics of Atypical Antipsychotic Drug

1
Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 42421, Saudi Arabia
2
Department of Pharmaceutics and Industrial Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt
Pharmaceutics 2020, 12(4), 297; https://doi.org/10.3390/pharmaceutics12040297
Received: 21 February 2020 / Revised: 18 March 2020 / Accepted: 23 March 2020 / Published: 25 March 2020
(This article belongs to the Section Clinical Pharmaceutics)
This study investigates the pharmacokinetic (PK) and pharmacodynamic (PD) consequences of shifting from Quetiapine fumarate immediate-release (IR) to extended-release (XR) formulation in non-adherent schizophrenia patients. Monte-Carlo simulations using population PK and PD models were implemented to predict the time course of plasma concentration and Brief Psychiatric Rating Scale (BPRS) scores following the oral administration of 200 mg Seroquel® every 12 h and 400 mg Seroquel XR® every 24 h in patients experiencing dose delay, omission or doubling. Parameters were computed and their distributions were compared using the Kolmogorov–Smirnov test. Dose irregularities with both formulations had different effects on plasma concentration and %reduction in BPRS scores from baseline. However, the odds ratio of getting a %reduction in BPRS below 14%, or plasma concentration exceeding 500 µg/L, were comparable for adherent and non-adherent patients. Plasma therapeutic concentration after treatment cessation was maintained for <24 h in 48% and 29.6% of patients, and a steady state recovery time of <48 h was achieved in 51% and 13.4% of patients on the IR and XR formulations, respectively. Monte-Carlo simulations predict that the risks associated with the IR dose irregularities are not worsened when the XR formulation is used instead. Non-adherence events involving a single dose of either formulation do not require rescue doses. View Full-Text
Keywords: antipsychotic; schizophrenia; pharmacokinetic/pharmacodynamic modeling; compliance; Monte Carlo simulations; extended-release antipsychotic; schizophrenia; pharmacokinetic/pharmacodynamic modeling; compliance; Monte Carlo simulations; extended-release
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MDPI and ACS Style

Elkomy, M.H. Changing the Drug Delivery System: Does it Add to Non-Compliance Ramifications Control? A Simulation Study on the Pharmacokinetics and Pharmacodynamics of Atypical Antipsychotic Drug. Pharmaceutics 2020, 12, 297.

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