Pharmacokinetics phase

Drugp act in various ways in the body. Oral drugp go through three phases the pharmaceutic phase, pharmacokinetic phase, and pharmacodynamic phase Liquid and parenteral drug (drug given by injection) go through the later two phases only. 

We thus have a series of unbound drug affinity measures relating to the action of the drug. The values are those typically obtained by the pharmacologist and form the basis of the structure-activity relationships which the medicinal chemist will work on. It is possible to extend this model to provide a pharmacokinetic phase as shown in Figure 2.9. 

Dmg transport during the pharmacokinetic phase represents a compromise between the increased solubility of the ionized form of a drug and the increased ability of the non-ionized form to penetrate the lipid bilayer of cell membranes. A drug must cross many lipid barriers as it travels to the receptor that is its site of action. Yet cell membranes... 

The cost of generic substitutes is usually considerably less than that for the trade name psychotropic drugs, but issues of bioequivalence must also be considered (see the section The Four Primary Pharmacokinetic Phases in Chapter 3). Using the fewest tablets to achieve a targeted dose level is always less expensive. Unit dose systems, sustained release preparations, and concentrate forms all increase the cost ( 26). 

The pharmacokinetics of a drug can also change with aging and disease (8, 20, 26, 29, 32, 64, 65, 66, 67, 68, 69 and 70). Several factors can alter the pharmacokinetic phases in the elderly, making them more prone to psychotropics effects, including the following ... 

This phenomenon can also occur with diseases that alter the physiological mechanisms subserving the various pharmacokinetic phases. 

VIII. Clinical evaluation Humans Phase I Safety and pharmacokinetics Phase II Initial clinical efficacy Phase III Clinical efficacy Phase IV Post-marketing trials... 

The pharmacokinetic phase of drug action includes the Absorption, Distribution, Metabolism and Elimination (ADME) of the drug. Many of the factors that influence drug action apply to all aspects of the pharmacokinetic phase. Solubility (see Section 3.3), for example, is an important factor in the absorption, distribution and elimination of a drug. Furthermore, the rate of drug dissolution, that is, the rate at which a solid drug dissolves in the aqueous medium, controls its activity when a solid drug is administered by enteral routes (see Section 2.6) as a solid or suspension. 

Define the terms pharmacokinetic phase and pharmacodynamic phase in the context of drug action. List the main general factors that affect these phases. 

For definitions see Section 2.7. The factors affecting the pharmacokinetic phase are ADME. The factor affecting the pharmacodynamic phase is the stereoelectronic structure of the drug molecule. 

In both pharmacokinetic and pharmacodynamic considerations, an important emphasis concerns the rate at which events occur and the rate at which circumstances change. The pharmacokinetic phase covers the relationship between drug input and the concentration achieved over time. The pharmacodynamic phase covers the relationship between concentration and the therapeutic effect over time (toxicodynamics is concerned with the relationship between concentration and adverse effects over time). 

This pharmacokinetic phase/pharmacodynamic phase model of dose-response can be described physiologically by considering each component of the phase as being separated by lipid membrane barriers that divide essentially aqueous environments. 

Katsaros, D., Oletti, M. V., Rigault de la Longrais, I. A., Ferrero, A., Celano, A., Fracchioli, S., Donadio, M., Passera, R., Cattel, L., and Bumma, C. (2005), Clinical and pharmacokinetic phase II study of pegylated liposomal doxorubicin and vinorelbine in heavily pretreated recurrent ovarian carcinoma, Ann Oncol, 16,300-306. 

Impact on the absorption of dmgs from the gastrointestinal tract (pharmacokinetic phase)... 

With regard to the pharmacokinetic phase of action, a distinction can be made between distribution over the various compartments or tissues, and the time-concentration relationship in particular compartments. Modulation of the pharmacokinetics by suitable molecular manipulation is important at an early stage in the design procedure. Here a distinction can be made between the modulation of the rate and possibly the site of bioinactivation or bioactivation, and modulation of the distribution, including the rate of absorption and rate of elimination. 

---