Physiologically-Based Pharmacokinetics
External control of tissues and cells, by hormones, nerves, and other stimuli, involves the transduction of signals from ligand-activated receptors to control of rate-limiting enzymes or proteins that affect key steps in metabolism, gene transcription or
- PDF / 1,018,011 Bytes
- 26 Pages / 439.37 x 666.142 pts Page_size
- 105 Downloads / 173 Views
Physiologically-Based Pharmacokinetics Masoud Jamei, Karen R. Yeo, Trevor N. Johnson, Cyrus Ghobadi, Manoranjenni Chetty, Khaled Abduljalil, Gaohua Lu, Farzaneh Salem, Adam Darwich, and Amin Rostami-Hodjegan
This chapter provides some background to physiologicallybased pharmacokinetic (PBPK) modeling and addresses the recent developments which have led to resurgence of using PBPK, particularly in relation to in vitro–in vivo extrapolation (IVIVE).
16.1 Building Blocks of Pharmacokinetics Pharmacokinetics (PK) deals with quantitative assessment of the fate of drugs in the body. Mathematical models are necessary to describe and predict concentrationtime profiles from data obtained by measuring the drug level in biological fluids such as blood, plasma, and urine. The models can range from simple compartmental analysis to very sophisticated Physiological Based Pharmacokinetics (PBPK) [11]. Among many other factors, the therapeutic outcome of drug treatment, depends on adequate exposure of the target cells as defined by the temporal variation M. Jamei K.R. Yeo C. Ghobadi M. Chetty K. Abduljalil G. Lu Simcyp Limited, Blades Enterprise Centre, John Street, Sheffield S2 4SU, UK e-mail: [email protected]; [email protected]; [email protected]; [email protected]; [email protected] T.N. Johnson Simcyp Limited, Blades Enterprise Centre, John Street, S2 4SU, Sheffield, UK e-mail: [email protected] F. Salem A. Darwich A.R.-Hodjegan () School of Pharmacy and Pharmaceutical Sciences, Faculty of Medical and Human Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester, UK e-mail: [email protected]; [email protected]; [email protected] E. Mosekilde et al. (eds.), Biosimulation in Biomedical Research, Health Care and Drug Development, DOI 10.1007/978-3-7091-0418-7 16, © Springer-Verlag/Wien 2012
361
362
M. Jamei et al.
of the drug concentration. Absorption, distribution, metabolism and excretion (ADME) of drugs can determine various features of their concentration-time profile. Traditionally, suitability of ADME characteristics for new drug candidates is established via quantitative-structure-property-relationship (QSPR), investigation of ADME in laboratory animals or by experiments involving in vitro systems. Many pharmaceutical scientists are well accustomed to simple linear models which use the data from above studies to determine and understand the ADME characteristics of drug candidates. However, the value associated with more integrated and complex modeling techniques which combines various pieces of information is not well recognized [55, 60]. Part of the perceived problem is the multi-scale nature of these models [66] which necessitates the presence of various expertise within a modeling team to help with creation, assessment and validation of the elements from each model and the inter-link between these models. The efforts in integration of various pieces of information in the field of pharmacokinetics and pharmacology
Data Loading...
