Pharmaceutical research
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Pharmaceutical research · May 2016
A Pharmacokinetic-Pharmacodynamic Model of Morphine Exposure and Subsequent Morphine Consumption in Postoperative Pain.
To characterize the pharmacokinetic-pharmacodynamic (PK-PD) relationship between exposure of morphine and subsequent morphine consumption and to develop simulation tools for model validation. ⋯ This study demonstrates the first quantitative link between exposure of morphine and subsequent morphine consumption and introduces an efficient visual predictive check approach with simulation of adaptive dosing.
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Pharmaceutical research · Apr 2016
Translational Modeling in Schizophrenia: Predicting Human Dopamine D2 Receptor Occupancy.
To assess the ability of a previously developed hybrid physiology-based pharmacokinetic-pharmacodynamic (PBPKPD) model in rats to predict the dopamine D2 receptor occupancy (D2RO) in human striatum following administration of antipsychotic drugs. ⋯ The rat hybrid PBPKPD model structure, integrated with in vitro information and human pharmacokinetic and physiological information, constitutes a scientific basis to predict the time course of D2RO in man.
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Pharmaceutical research · Oct 2014
Handling missing data in a duloxetine population pharmacokinetic/pharmacodynamic model - imputation methods and selection models.
In pharmacokinetic (PK)/pharmacodynamic (PD) modelling and simulations (M&S), omitting dropouts can cause inaccuracies in parameter estimation and clinical trial simulations (CTS). This study examines the impact of different imputation methods for missing data on the interpretation of model results, as well as develops a selection model (where dropout and efficacy are jointly modelled) for use in CTS. ⋯ Missing data had little impact on the original population PK/PD analyses. Sensitivity analyses for dropouts should be conducted in M&S exercises. The utility of selection models in CTS was explored via a hypothetical case study.
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Pharmaceutical research · Mar 2014
ReviewOvercoming the blood-brain barrier in chemotherapy treatment of pediatric brain tumors.
Pediatric brain tumors are most common cancers in childhood and among the leading causes of death in children. Chemotherapy has been used as adjuvant (i.e. after) or neoadjuvant (i.e. before) therapy to surgery and radiotherapy for the management of pediatric brain tumors for more than four decades and gained more attention in the recent two decades. ⋯ Therefore, various strategies have been developed and used to address this issue. Herein, we review different methods reported in the literature to circumvent the BBB for enhancing the present of chemotherapeutics in the brain to treat pediatric brain tumors.
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Pharmaceutical research · Mar 2014
Semi-mechanistic modelling of the analgesic effect of gabapentin in the formalin-induced rat model of experimental pain.
The formalin-induced rat model of nociception involves moderate continuous pain. Formalin-induced pain results in a typical repetitive flinching behaviour, which displays a biphasic pattern characterised by peaks of pain. Here we described the time course of pain response and the analgesic effect of gabapentin using a semi-mechanistic modelling approach. ⋯ A compartmental, semi-mechanistic model provides the basis for further understanding of the formalin-induced flinching response and consequently to better characterisation of the properties of gabapentin, such as the potency in individual animals. Moreover, despite high exposure levels, model predictions show that gabapentin does not completely suppress behavioural response in the formalin-induced pain model.