| Title | Simple physicochemical properties as effective filters for risk estimation of drug transport across the human placental barrier | ||
| Authors | C. Giaginis1,2, A. Zira1,2, S. Theocharis2 and A. Tsantili-Kakoulidou1
1. Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimioupolis, Zografou, Athens, Greece 2. Department of Forensic Medicine and Toxicology, Medical School, University of Athens, 75 Mikras Asias Street, Athens, Greece. |
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| Citation | Giaginis, C., Zira, A., Theocharis, S., Tsantili-Kakoulidou, A.: Simple physicochemical properties as effective filters for risk estimation of drug transport across the human placental barrier, Epitheorese Klin. Farmakol. Farmakokinet. 22(2): 146-148 (2008) | ||
| Publication Date | 23-25 May 2008 | ||
| Full Text Language | English | ||
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| Keywords | Placental transfer, clearance index, ADME/Tox properties, physicochemical, molecular descriptors. | ||
| Other Terms | Review article | ||
| Summary | Pharmacological agents and environmental pollutants can be transferred from mother to fetus across the placental barrier leading to reproductive toxic effects. Several in vitro, in vivo and ex vivo experimental models have been developed to study this process. However, such techniques are tedious and time-consuming, while they suffer from serious drawbacks during experimentation procedure. Thus, the establishment of computational classification and prediction models may be considered as a promising tool to support high throughput screening of chemicals in respect to their transport across the human placenta. Such in silico techniques have already defined cut off values or ranges for certain molecular properties related to absorption, distribution, metabolism, elimination (ADME) characteristics of drugs. Among them, the rule of 5 (ROF) comprises molecular weight, lipophilicity, hydrogen bond donor and acceptor sites, as essential molecular characteristics for the estimation of oral drug permeability. In the current study these molecular characteristics served as a basis, in order to establish relevant criteria for minimization of the placental transfer risk. A data set of 94 compounds with literature available placental transfer data, expressed by clearance index (CI) was compiled. Molecular properties were calculated by widely recognized software packages. Data were divided into low and high placental transfer groups, considering CI = 0.3. The scatter plots between the calculated descriptors and the CI values were constructed, cut off values were proposed and the percentage of low or high placental transfer cases beyond these values was assessed. Generally, compounds with high molecular weight and with a relatively high number of hydrogen bond sites and thereupon a low lipophilicity, may exhibit reduced transport across the placental barrier. | ||
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| Relative Papers | |||
Online ISSN 1011-6575
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Articles published in this Journal are Indexed or Abstracted in: • Chemical Abstracts • Elsevier’s Bibliographic Databases: Scopus, EMBASE, EMBiology, Elsevier BIOBASE SCImago Journal and Country Rank Factor
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