Development and validation of a physiology-based model for the prediction of pharmacokinetics/toxicokinetics in rabbits

نویسندگان

  • Panteleimon D Mavroudis
  • Helen E Hermes
  • Donato Teutonico
  • Thomas G Preuss
  • Sebastian Schneckener
چکیده

The environmental fates of pharmaceuticals and the effects of crop protection products on non-target species are subjects that are undergoing intense review. Since measuring the concentrations and effects of xenobiotics on all affected species under all conceivable scenarios is not feasible, standard laboratory animals such as rabbits are tested, and the observed adverse effects are translated to focal species for environmental risk assessments. In that respect, mathematical modelling is becoming increasingly important for evaluating the consequences of pesticides in untested scenarios. In particular, physiologically based pharmacokinetic/toxicokinetic (PBPK/TK) modelling is a well-established methodology used to predict tissue concentrations based on the absorption, distribution, metabolism and excretion of drugs and toxicants. In the present work, a rabbit PBPK/TK model is developed and evaluated with data available from the literature. The model predictions include scenarios of both intravenous (i.v.) and oral (p.o.) administration of small and large compounds. The presented rabbit PBPK/TK model predicts the pharmacokinetics (Cmax, AUC) of the tested compounds with an average 1.7-fold error. This result indicates a good predictive capacity of the model, which enables its use for risk assessment modelling and simulations.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Effects of Ethanol on the Toxicokinetics of Methamphetamine in Rabbits

In the current study, the effects of ethanol (EtOH) on toxicokinetics of methamphetamine (MA) and its metabolite amphetamine (AP) were investigated. A single dose of MA hydrochloride at 15 mg/Kg was given intragastrically, either alone (MA group; n = 8) or in conjunction with 3 g/Kg EtOH (MA+EtOH group; n = 8) to rabbits. In placebo group, normal saline only was given (placebo group; n = 4). Pl...

متن کامل

Pavement performance prediction model development for Tehran

Highways and in particular their pavements are the fundamental components of the road network. They require continuous maintenance since they deteriorate due to changing traffic and environmental conditions. Monitoring methods and efficient pavement management systems are needed for optimizing maintenance operations. Pavement performance prediction models are useful tools for determining the op...

متن کامل

Quantitative Modeling for Prediction of Critical Temperature of Refrigerant Compounds

The quantitative structure-property relationship (QSPR) method is used to develop the correlation between structures of refrigerants (198 compounds) and their critical temperature. Molecular descriptors calculated from structure alone were used to represent molecular structures. A subset of the calculated descriptors selected using a genetic algorithm (GA) was used in the QSPR model development...

متن کامل

Effects of Ethanol on the Toxicokinetics of Methamphetamine in Rabbits

In the current study, the effects of ethanol (EtOH) on toxicokinetics of methamphetamine (MA) and its metabolite amphetamine (AP) were investigated. A single dose of MA hydrochloride at 15 mg/Kg was given intragastrically, either alone (MA group; n = 8) or in conjunction with 3 g/Kg EtOH (MA+EtOH group; n = 8) to rabbits. In placebo group, normal saline only was given (placebo group; n = 4). Pl...

متن کامل

Improved Mathematical Model for Helicopters Flight Dynamics Applications

The purpose of this paper is concerned with the mathematical model development issues, necessary for a better prediction of dynamic responses of articulated rotor helicopters. The methodology is laid out based on mathematical model development for an articulated rotor helicopters, using the theories of aeroelastisity, finite element and the time domain compressible unsteady aerodynamics. The he...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 13  شماره 

صفحات  -

تاریخ انتشار 2018