Amin Rostami-Hodjegan

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Adverse reactions to polysubstance misuse are common in nightclubs, yet little is known of the physiological effects of polysubstance misuse in this environment. This study examined the heart rate, blood pressure and oral temperature of 50 participants recruited in a nightclub on four separate nights. In addition, the increase in environmental temperature(More)
The perceived failure of new drug development has been blamed on deficiencies in in vivo studies of drug efficacy and safety. Prior simulation of the potential exposure of different individuals to a given dose might help to improve the design of such studies. This should also help researchers to focus on the characteristics of individuals who present with(More)
Pharmacokinetic models range from being entirely exploratory and empirical, to semi-mechanistic and ultimately complex physiologically based pharmacokinetic (PBPK) models. This choice is conditional on the modelling purpose as well as the amount and quality of the available data. The main advantage of PBPK models is that they can be used to extrapolate(More)
The aim of this study was to model the in vivo kinetic consequences of mechanism-based inhibition (MBI) of CYP2D6 by 3,4 methylenedioxymethamphetamine (MDMA, ecstasy). A model with physiologically-based components of drug metabolism was developed, taking account of change in the hepatic content of active CYP2D6 due to MBI by MDMA. Based on the in vitro(More)
The measurement of plasma clozapine concentrations is useful in assessing compliance, optimizing therapy, and minimizing toxicity. We measured plasma clozapine and norclozapine (N-desmethylclozapine) concentrations in samples from 3782 patients (2648 male, 1127 female). No clozapine was detected in 291 samples (227 patients, median prescribed dose 300(More)
Typically, pharmacokinetic-pharmacodynamic (PK/PD) models use plasma concentration as the input that drives the PD model. However, interindividual variability in uptake transporter activity can lead to variable drug concentrations in plasma without discernible impact on the effect site organ concentration. A physiologically based PK/PD model for(More)
BACKGROUND AND OBJECTIVES The interplay between liver metabolising enzymes and transporters is a complex process involving system-related parameters such as liver blood perfusion as well as drug attributes including protein and lipid binding, ionisation, relative magnitude of passive and active permeation. Metabolism- and/or transporter-mediated drug-drug(More)
The utilisation of physiologically-based pharmacokinetic models for the analysis of population data is an approach with progressively increasing impact. However, as we move from empirical to complex mechanistic model structures, incorporation of stochastic variability in model parameters can be challenging due to the physiological constraints that may(More)
This study aimed to demonstrate the added value of integrating prior in vitro data and knowledge-rich physiologically based pharmacokinetic (PBPK) models with pharmacodynamics (PDs) models. Four distinct applications that were developed and tested are presented here. PBPK models were developed for metoprolol using different CYP2D6 genotypes based on in(More)
To develop a population physiologically-based pharmacokinetic (PBPK) model for simvastatin (SV) and its active metabolite, simvastatin acid (SVA), that allows extrapolation and prediction of their concentration profiles in liver (efficacy) and muscle (toxicity). SV/SVA plasma concentrations (34 healthy volunteers) were simultaneously analysed with NONMEM(More)