Pharmacokinetic considerations drug distribution pharmacological

Many factors have a profound influence on the pharmacokinetics of drugs and consequently on a patient s pharmacological response (Box 33-1). For example, the consideration of the patient s history, with particular emphasis on theirpathophysiological state and adjunct drug therapy, is essential at the initiation of drug therapy and TDM. Other important factors include how a drug is absorbed, distributed, metabolized, cleared by the Liver, biotransformed, and excreted. 

The onset, duration, and intensity of action of a drug after administration are controlled by the rate at which the drug reaches its site of action and by the concentration of the drug at the receptor. The physiological disposition of a drug is controlled by the three major processes of absorption, distribution into and within tissues, and elimination. Pharmacokinetics is a mathematical consideration of these processes which relates the dose given, the concentration in the blood, and the pharmacological response. 

Fig. 1. Overview of pharmacology. Pharmacokinetics (PK) relates to the effect of the body on the drug and principally includes bioavailability, distribution, and clearance. Pharmacodynamics (PD) relates to drug concentration and receptor availability. The response to drug concentrations may be therapeutic, subtherapeutic, or toxic, depending on considerations involving both PK and PD principles. From Linder MW, Valdes R Jr. Pharmacogenetics fundamentals and applications. Therapeutic drug monitoring and toxicology. AACC 1999 20(l) 10 with permission.)...

The concept behind the use of liposomes as carriers of drugs and macromolecules is related to an expected protection of the encapsulated molecules in the blood stream, an altered tissue distribution and pharmacokinetics, as well as an increased uptake into cells by mechanisms that are not normally available for these molecules. Some of these expectations have been verified through studies in various laboratories during the last few years. Such studies have shown that liposome encapsulation can alter drastically the pharmacokinetics and tissue disposition of the encapsulated substances, it can enhance their uptake into cells, and it can Increase their pharmacological efficacy. Several recent reviews have discussed these early results in considerable detail. 20... 

---