PMID- 20843296
OWN - NLM
STAT- MEDLINE
DCOM- 20110310
LR  - 20191111
IS  - 1875-6220 (Electronic)
IS  - 1570-1638 (Linking)
VI  - 7
IP  - 3
DP  - 2010 Sep
TI  - Integration of physicochemical and pharmacokinetic parameters in lead 
      optimization: a physiological pharmacokinetic model based approach.
PG  - 143-53
AB  - There have been major strides in the development of novel ways of investigating 
      drug like properties of new chemical entities (NCE) in the last three decades. 
      Identification of ideal properties of a clinical candidate that would give a 
      clinical proof of concept (POC) is the most critical step in the discovery 
      process. Besides the biological dose-response relationship, the pharmacokinetic 
      parameters play the most vital role in influencing the therapeutic response or 
      toxicity of NCE. While there are numerous techniques to understand various 
      drug-like properties individually, the behavior of an NCE in a dynamic in vivo 
      system which influences its therapeutic or toxic effects is a composite function 
      of its various physicochemical and pharmacokinetic parameters. This implies the 
      need to understand the collective influence of various measured parameters, and 
      knowing how variations made in them can result in favorable pharmacodynamic or 
      toxicokinetic properties. Understanding this behavior holds the key to a 
      successful and time efficient lead optimization process. Physiological based 
      pharmacokinetic models (PBPK) are of great interest in this context as they 
      involve a natural way of integrating the individual compound property to 
      physiological properties, providing a rational approach to predict drug like 
      behavior (an ideal behavior identified may be addressed generally as Target 
      Product Profile) in vivo. In the current review, various physiological 
      pharmacokinetic models addressing absorption, tissue distribution and clearance 
      are discussed along with their application in integrating various physicochemical 
      and ADME parameters to predict human pharmacokinetics helping lead optimization.
FAU - Benjamin, Biju
AU  - Benjamin B
AD  - Metabolism and Pharmacokinetics, New Drug Discovery Research, Ranbaxy Research 
      Laboratories, Plot- 20, Sector-18, Udyog Vihar Industrial Area, Gurgaon, Haryana, 
      India. bijub_2000@yahoo.com
FAU - Barman, Tarani Kanta
AU  - Barman TK
FAU - Chaira, Tridib
AU  - Chaira T
FAU - Paliwal, Jyoti K
AU  - Paliwal JK
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Drug Discov Technol
JT  - Current drug discovery technologies
JID - 101157212
RN  - 0 (Pharmaceutical Preparations)
SB  - IM
MH  - Absorption/physiology
MH  - Animals
MH  - Drug Evaluation, Preclinical/methods
MH  - Humans
MH  - Metabolic Clearance Rate
MH  - *Models, Biological
MH  - Pharmaceutical Preparations/chemistry/*metabolism
MH  - *Pharmacokinetics
MH  - Tissue Distribution
EDAT- 2010/09/17 06:00
MHDA- 2011/03/11 06:00
CRDT- 2010/09/17 06:00
PHST- 2010/06/30 00:00 [received]
PHST- 2010/07/20 00:00 [accepted]
PHST- 2010/09/17 06:00 [entrez]
PHST- 2010/09/17 06:00 [pubmed]
PHST- 2011/03/11 06:00 [medline]
AID - ABSTRACT # 25 [pii]
AID - 10.2174/157016310793180558 [doi]
PST - ppublish
SO  - Curr Drug Discov Technol. 2010 Sep;7(3):143-53. doi: 10.2174/157016310793180558.