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Drugs in pregnancy and lactation
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Most drugs cross from maternal blood to milk by passive diffusion of unionised free drug. This passive diffusion is driven by a concentration gradient, established when there is a difference in the concentration of chemicals on either side of a semi-permeable membrane. The rate of diffusion depends on the physico-chemical characteristics of the drug.
Homeostasis of Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
Small molecules can penetrate the cell membrane through two major processes: passive diffusion and carrier-mediated transport [36]. In general, lipophilic substances have high membrane permeability and move across the cell membrane down their concentration gradients without a need for energy input. Hydrophilic substances, on the other hand, have low membrane permeability, and their efficient uptake into the cell requires a carrier-mediated transport. The latter must be coupled to an energy source to power the uphill transport of a given compound against its concentration gradient. In addition, carrier-mediated transport is saturable, inhibitable, and depends on the specific properties of the transporters expressed in a given tissue or cell type. Clinically, transporters are of great attraction for the development of specific drugs and also for understanding interindividual variability in drug responsiveness.
Toxicokinetics
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
The simplest mechanism for the transportation of molecules involves diffusion, defined as the transport of molecules across a semi-permeable membrane. The most common pathway of diffusion is passive transport. In passive transport, molecules are transported from an area of high to low solute concentration—that is, down the concentration gradient. It is not an energy-dependent process, and no electrical gradient is generated. Lipophilic molecules, small ions, and electrolytes generally gain access through membrane compartments by passive diffusion, since they are not repelled by the phospholipid bilayer of the cell membrane. Most passive diffusion processes, however, are not molecularly selective.
F7 and topotecan co-loaded thermosensitive liposome as a nano-drug delivery system for tumor hyperthermia
Published in Drug Delivery, 2020
Chunyang Du, Shuangshuang Li, Yuan Li, Hervé Galons, Na Guo, Yuou Teng, Yongmin Zhang, Mingyuan Li, Peng Yu
Synchronous release of both drugs can optimize synergy. In this study, the in vitro release data deviated from the ideal state at 41 °C. When the TSLs were at the phase transition temperature, TPT release was accelerated, whereas that of F7 was not significantly affected (Figure 4). However, simple in vitro release does not simulate the pattern of drugs in the body. Passive diffusion through lipid membranes is a common mode of transport of fat-soluble drugs. Besides, liposomes can enter cells by endocytosis, membrane fusion, and other mechanisms. Thus, encapsulated drugs can be delivered to the cells simultaneously. Based on the in vivo environment and methods of liposome entry into cells, the F7-TPT-TSL formulation was located in the tumor tissue and the loaded drugs were synchronized. The MTT assay validated the synergistic effects of the drugs (Figure 8).
Challenges with the precise prediction of ABC-transporter interactions for improved drug discovery
Published in Expert Opinion on Drug Discovery, 2018
It has long been perceived that the movement of solutes across the cell membrane is accomplished through transcellular passive diffusion. However, this observation has changed over the last two decades, and the membrane transporters expressed in various tissues and organs are recognized to have a vital role in the control of solutes in and out of the cells. These transporters perform key functions in the absorption, distribution, and excretion of exogenous and endogenous compounds. The solute carrier family includes most of the uptake transporters, while the ATP-binding cassette (ABC) family includes the majority of the efflux transporters. The ABC transporters actively utilize the energy from ATP hydrolysis to convey substrates across cell membranes. Transporters in this family include P-glycoprotein (P-gp), or MDR1, (ABCB1), bile salt export pump (BSEP, ABCB11), breast cancer resistance protein (BCRP, ABCG2), and the multidrug resistance-associated proteins (MRPs, ABCCs) (Figure 1). Physiological roles for these ABC transporters include the export of compounds from cells into extracellular spaces, renal and hepatic drug clearance, efflux of endogenous and endogenous compounds, and disposition of bile salts from the liver into the bile.
Advances in cell-based permeability assays to screen drugs for intestinal absorption
Published in Expert Opinion on Drug Discovery, 2020
The intestinal epithelium comprises a major obstacle for drug absorption, which is comprised of absorptive and other functional cells, with its physical (cell wall layers, mucus) and biochemical (metabolism, efflux, uptake) barrier functions [4]. Drugs cross the intestinal membrane via different pathways based on their physicochemical properties [5]. Passive diffusion is gradient driven, comprised of paracellular and transcellular components. The paracellular route is restricted by tight junctions and is generally used by low molecular weight hydrophilic compounds. Lipophilic compounds partition from the lumen into the cell membrane by the transcellular pathway. Active, or carrier-mediated, transport involves the uptake of a drug into or efflux out of the enterocytes.