Pharmacokinetics encompasses the processes of absorption, distribution, deposition, transformation and excretion of medicinal substances (MSs). To reach the required organ or target cell, the MS has to be absorbed into the bloodstream passing through the gastrointestinal tract mucosa (in the event of oral intake) or through the blood vessel wall (in the event of parenteral administration), and then it should leave the bloodstream to render a pharmacological effect. In this case from the point of view of the body, the medication is a xenobiotic chemical compound that has to be transformed (metabolized) into a hydrophilic metabolite (highly soluble substance), and then excreted.
2.1. ABSORPTION
There are four ways for a substance to pass through the biological membranes (listed in the order of frequency of use in pharmacology):
• diffusion (passive or facilitated);
• paracellular transport (also referred to as filtration);
• active transport;
• pinocytosis, endocytosis.
Passive diffusion is the predominant mechanism of drug transport across cell membranes along a concentration gradient. Since cell membranes are mostly composed of lipids, lipophi-lic nonpolar substances, i.e. highly lipid-solu-ble substances that have no electrical charge (fig. 2.1) can easily penetrate the membrane via passive diffusion.
According to Fick's law of diffusion, the flux of drug across the membrane is equal to:
flux = (C2-C1) × S × membrane permeability / thickness,
where С1 and С2 are intracellular and extracellular drug concentrations, respectively; S - membrane area.
On the contrary, hydrophilic polar substances, i.e. highly water-soluble substances that have an electrical charge, cannot cross the cell membrane easily through passive diffusion (see