The role of the placenta in drug transport and fetal drug exposure

2018 ◽  
Vol 11 (4) ◽  
pp. 373-385 ◽  
Author(s):  
Gideon Koren ◽  
Asher Ornoy
Keyword(s):  
Drug Transport ◽  
Drug Exposure ◽  
Fetal Drug Exposure

Methodological Approaches to Evaluate Fetal Drug Exposure

2019 ◽  
Vol 25 (5) ◽  
pp. 496-504 ◽  
Author(s):  
Naïm Bouazza ◽  
Frantz Foissac ◽  
Déborah Hirt ◽  
Saïk Urien ◽  
Sihem Benaboud ◽  
...  
Keyword(s):  
Cord Blood ◽  
Drug Exposure ◽  
Placental Transfer ◽  
Ex Vivo ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Pbpk Models ◽  
Drug Concentrations ◽  
Fetal Drug Exposure

Background: Drug prescriptions are usual during pregnancy, however, women and their fetuses still remain an orphan population with regard to drugs efficacy and safety. Most xenobiotics diffuse through the placenta and some of them can alter fetus development resulting in structural abnormalities, growth or functional deficiencies. Methods: To summarize the different methodologies developed towards the prediction of fetal drug exposure. Results: Neonatal cord blood concentration is the most specific measurement of the transplacental drug transfer at the end of pregnancy. Using the cord blood and mother drug concentrations altogether, drug exchanges between the mother and fetus can be modeled and quantified via a population pharmacokinetic analysis. Thereafter, it is possible to estimate the fetus exposure and the fetus-to-mother exposure ratio. However, the prediction of placental transfer before any administration to pregnant women is desirable. Animal studies remain difficult to interpret due to structural and functional inter-species placenta differences. The ex-vivo perfusion of the human placental cotyledon is the method of reference to study the human placental transfer of drugs because it is thought to mimic the functional placental tissue. However, extrapolation of data to in vivo situation remains difficult. Some research groups have extensively worked on physiologically based models (PBPK) to predict fetal drug exposure and showed very encouraging results. Conclusion: PBPK models appeared to be a very promising tool in order to predict fetal drug exposure in-silico. However, these models mainly picture the end of pregnancy and knowledge regarding both, development of the placental permeability and transporters is strongly needed.

scholarly journals Role of Liposomes Composite as Drug Transport Mechanism

2021 ◽  
pp. 230-243
Keyword(s):  
Drug Delivery ◽  
Lipid Bilayers ◽  
Transport Mechanism ◽  
Drug Transport ◽  
Phospholipid Bilayer ◽  
Drug Transporter ◽  
Delivery Methods ◽  
Second Stage ◽  
Novel Drug

Liposomes are spherical shaped vesicles comprising of at least one phospholipid bilayer that serve as a novel drug delivery framework. They are microscopic structures in which a fluid system is totally encased by a film made out of lipid bilayers. It varies in size, conformation, charge and drug transporter stacked with assortment of particles, for example, small molecules of drug, plasmids, nucleotides or proteins and so on. Ongoing advances in nanotherapeutics have brought about engineered liposomes rising in nanomedicine, giving better restorative control of diseased states. This has made ready for the improvement of second-stage liposomes for increased efficiency and could at last lead to a change in perspective from the regular drug delivery methods.

The Placenta as a Functional Barrier to Fetal Drug Exposure

The Placenta ◽  
2011 ◽  
pp. 303-309
Author(s):  
Tatiana N. Nanovskaya ◽  
Gary D. V. Hankins ◽  
Mahmoud S. Ahmed
Keyword(s):  
Drug Exposure ◽  
Fetal Drug Exposure

Multiscale homogenization for fluid and drug transport in vascularized malignant tissues

2014 ◽  
Vol 25 (01) ◽  
pp. 79-108 ◽  
Author(s):  
R. Penta ◽  
D. Ambrosi ◽  
A. Quarteroni
Keyword(s):  
Drug Transport ◽  
Reaction Model ◽  
Diffusion Reaction ◽  
Momentum Balance ◽  
Cancer Therapies ◽  
Multiscale Expansion ◽  
Anti Cancer ◽  
Intercapillary Distance ◽  
Multiscale Homogenization

A system of differential equations for coupled fluid and drug transport in vascularized (malignant) tissues is derived by a multiscale expansion. We start from mass and momentum balance equations, stated in the physical domain, geometrically characterized by the intercapillary distance (the microscale). The Kedem–Katchalsky equations are used to account for blood and drug exchange across the capillary walls. The multiscale technique (homogenization) is used to formulate continuum equations describing the coupling of fluid and drug transport on the tumor length scale (the macroscale), under the assumption of local periodicity; macroscale variations of the microstructure account for spatial heterogeneities of the angiogenic capillary network. A double porous medium model for the fluid dynamics in the tumor is obtained, where the drug dynamics is represented by a double advection–diffusion–reaction model. The homogenized equations are straightforward to approximate, as the role of the vascular geometry is recovered at an average level by solving standard cell differential problems. Fluid and drug fluxes now read as effective mass sources in the macroscale model, which upscale the interplay between blood and drug dynamics on the tissue scale. We aim to provide a theoretical setting for a better understanding of the design of effective anti-cancer therapies.

scholarly journals Bmal1 regulates circadian expression of cytochrome P450 3a11 and drug metabolism in mice

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Yanke Lin ◽  
Shuai Wang ◽  
Ziyue Zhou ◽  
Lianxia Guo ◽  
Fangjun Yu ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Drug Exposure ◽  
Defense Mechanism ◽  
Critical Role ◽  
The Body ◽  
Cellular Regulation ◽  
Circadian Expression ◽  
Distal Promoter ◽  
Daily Time

Abstract Metabolism is a major defense mechanism of the body against xenobiotic threats. Here we unravel a critical role of Bmal1 for circadian clock-controlled Cyp3a11 expression and xenobiotic metabolism. Bmal1 deficiency decreases the mRNA, protein and microsomal activity of Cyp3a11, and blunts their circadian rhythms in mice. A screen for Cyp3a11 regulators identifies two circadian genes Dbp and Hnf4α as potential regulatory mediators. Cell-based experiments confirm that Dbp and Hnf4α activate Cyp3a11 transcription by their binding to a D-box and a DR1 element in the Cyp3a11 promoter, respectively. Bmal1 binds to the P1 distal promoter to regulate Hnf4α transcriptionally. Cellular regulation of Cyp3a11 by Bmal1 is Dbp- and Hnf4α-dependent. Bmal1 deficiency sensitizes mice to toxicities of drugs such as aconitine and triptolide (and blunts circadian toxicity rhythmicities) due to elevated drug exposure. In summary, Bmal1 connects circadian clock and Cyp3a11 metabolism, thereby impacting drug detoxification as a function of daily time.

scholarly journals Equine Drug Transporters: A Mini-Review and Veterinary Perspective

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1064
Author(s):  
Brielle Rosa
Keyword(s):  
Drug Transport ◽  
Drug Disposition ◽  
Drug Transporters ◽  
Transport Proteins ◽  
Pharmacokinetic Parameters ◽  
Transporter Protein ◽  
Drug Pharmacokinetic ◽  
Species Specific ◽  
And Function

Xenobiotic transport proteins play an important role in determining drug disposition and pharmacokinetics. Our understanding of the role of these important proteins in humans and pre-clinical animal species has increased substantially over the past few decades, and has had an important impact on human medicine; however, veterinary medicine has not benefitted from the same quantity of research into drug transporters in species of veterinary interest. Differences in transporter expression cause difficulties in extrapolation of drug pharmacokinetic parameters between species, and lack of knowledge of species-specific transporter distribution and function can lead to drug–drug interactions and adverse effects. Horses are one species in which little is known about drug transport and transporter protein expression. The purpose of this mini-review is to stimulate interest in equine drug transport proteins and comparative transporter physiology.

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