1. TOPICS TO DISCUSS
1. Pharmacokinetics. Definition.
2. Mechanisms of drug penetration through membranes. Dependence of a drug penetration on their lipid solubility. Penetration of weak acids and bases through cell membranes (dependence on the pH of the medium and the pKa).
3. Routes of drug administration. The main characteristics.
4. Drug absorption. Dependence of drug absorption on routes of administration. The main mechanisms of drug absorption after oral, intramuscular and subcutaneous administrations.
5. Bioavailability. Factors that influence bioavail-ability after oral administration. First-pass effect. Calculation of a drug bioavailability.
6. Distribution of drugs in the body. Penetration through the blood-brain barrier.
7. Accumulation of drugs in the body. Binding of drugs to plasma proteins.
8. Apparent volume of distribution: definition, dependence on drug concentration in body fluids.
9. Drug biotransformation (metabolism). Phase I and phase II reactions. The main changes in the properties of drugs (lipophilicity, hydrophilicity, activity, toxicity) caused by their metabolism.
10. Excretion of drugs. Routes of excretion.
11. The main pharmacokinetic parameters characterizing drug elimination: the rate constant for drug elimination, half-life, clearance.
Background information
Drug penetration through membranes
Typically drugs move from the site of administration to the site of action permeating through membranes that separate different compartments. The main mechanisms of penetration across membranes include:
• passive diffusion;
• active transport;
• facilitated diffusion;
• endocytosis/exocytosis.
Passive diffusion is driven by the concentration gradient of the permeating drug. Most lipophilic drugs easily penetrate lipid membranes by passive diffusion i.e. lipid diffusion. In this case lipid: water partition coefficient is a major determinant of drug penetration. Passive diffusion of hydrophilic substances i.e. aqueous diffusion through membrane aqueous pores that have small size is limited to extremely small molecules (e.g. urea) and is out of the value for most drugs.