Concentration of a drug

Half-life is the time taken to decrease the concentration of a drug to one-half its original value. There may be several phases in the elimination, and the most common is the so-called beta-phase. Alpha-phase is a distribution phase and gamma-phase is the terminal phase when the drug is finally leaving the tissues. 

In this technique the concentration of a drug in an agar plate may (theoretically) be varied infinitely between zero and a given maximum. To perform the test, nutrient agar is melted, the solution under test added, and the mixture poured into a sterile Petri dish and allowed to set in the form of a wedge (Fig. 11.6A). 

Minimum inhibitory concentration The lowest concentration of a drug that will visually inhibit the growth of a microorganism. 

This is the second of the two questions identified at the start of Section 1.2, where it was noted that the earliest pharmacologists had no choice but to use indirect methods in their attempts to account for the relationship between the concentration of a drug and the tissue response that it elicits. In the absence at that time of any means of obtaining direct evidence on the point, A. V. Hill and A. J. Clark explored the consequences of assuming (1) that the law of mass action applies, so that Eq. (1.2), derived above, holds and (2) that the response of the tissue is linearly related to receptor occupancy. Clark went further and made the tentative assumption that the relationship might be one of direct proportionality (though he was well aware that this was almost certainly an oversimplification, as we now know it usually is). 

The plasma concentration of a drug immediately following a 50-mg intravenous bolus dose of the drug was found to be 0.84 mcg/mL. What is the apparent volume of distribution of the drug ... 

K0 is the molar concentration of a drug at which 50% of its receptors are occupied at equilibrium (mmol.l ). 

In the laboratory, affinity can be measured as the concentration of a drug that occupies 50% of the available receptors, as suggested by the definition... 

The concentration of a drug that induces a specified response exactly halfway between baseline and maximum. 

The time taken for the plasma concentration of a drug to fall by half after the cessation of an infusion designed to maintain a steady plasma concentration (time). 

It is important to realize that the CSHT does not predict the time to patient awakening but simply the time until the plasma concentration of a drug has fallen by half. The patient may need the plasma concentration to fall by 75% in order to awaken, and the time taken for this or any other percentage fall to occur is known as a decrement time. 

Pharmacokinetic concentration-time curves for a drug and ifs mefabolifes are used to identify primary exposure metrics such as AUC, or which are not time-dependent unlike the sequential measurements of concentration over time. A peak plasma concentration of a drug is often associated with a PD response, especially with an adverse event. There can be large inter-individual variability in the time-to-peak concentration, and closely spaced sampling times are often critical to determining the peak plasma concentration accurately in individual patients because of differences in demographics, disease states, and food effects, if any. All these elements are clearly spelled out in the protocols written to conduct these studies. 

When the concentration of a drug cannot be directly related to effect, indirect modeling is suggested. This will most aptly apply to situations where, for example, the response is not directly a result of action (e.g., binding a receptor site) as there may be several steps involved in between the action and response with their own specific mathematical relationships. Unlike the direct action models where any delay in the response is likely a result of PK phenomenon, fhe delay where indirecf models are used is a result of intrinsic nature of drug action and response relationship. Several models can be used in such instances ... 

Several factors influence a drug s absorption (table 3.1). Aqueous solutions are more easily absorbed than a lipid solution or solid form. Absorption of drugs in solid form is affected by the rate at which it dissolves. Higher concentrations of a drug are more rapidly absorbed than low concentrations. The amount of blood flow to the site also influences absorption heat and vasodilators increase absorption. 

Type of solution (aqueous vs. lipid) Rate of dissolution of solid drugs Concentrations of a drug present Blood flow to the site of absorption Surface area of absorption... 

Unfortunately, few of the studies that have attempted to relate the blood concentrations of neuroleptics to therapeutic response have fulfilled all these criteria. There is a suggestion that a "thera peutic window" exists for some phenothiazine neuroleptics. A therapeutic window is a range of concentrations of a drug measured in the blood that are associated with a good therapeutic response. Plasma concentrations outside this range are either too low to ensure a therapeutic response or so high that they induce toxic side effects. Despite the numerous studies of the relationship between the plasma concentration and the therapeutic response for a number of "standard" neuroleptics, it would appear that such correlations rarely account for more than 25% of the variance in clinical response to treatment. The existence of a therapeutic window for neuroleptics would therefore appear to be unproven. However, there could be ranges of plasma concentrations associated with optimal antipsychotic action, but these... 

Age or body weight can affect the systemic availability of many antimicrobial agents. In the physically smaller animal (sheep and pig) the peak serum concentration of a drug is usually higher and is followed by a rapid decline compared with a lower peak and a slower decline of the antibiotic in seruon of the larger animal (cow and horse). The limited experimental data appear to indicate that the extent of systemic availability of IM-administored antibiotics can vary as widely between different sites as between IM and SC sites. A corollary to this observation is that the location of the extra-vascular injection site should be well-defined when determining the systemic availability of parenteral preparations (9). 

The relationship between the concentration of a drug and its effect is determined in order to define the range of active drug concentrations (potency) and the maximum possible effect (efficacy). 

It is not usually possible to measure the concentration of a drug at its sites of action. Plasma, which can be conveniently sampled, is generally used instead, but drug concentrations may be determined in other bodily fluids, such as saliva and cerebrospinal fluid, as well as, of course, the excreta, urine and faeces. There is often a relationship between plasma concentration and response, although this may sometimes... 

When creating a graph of the relationship between the time course of the plasma concentrations of a drug in the body (plotted on the x-axis) and the time course of the observed drug effect (plotted on the y-axis), a loop with a counterclockwise direction may be obtained. This means that there are more than two values of effect that correspond to a single plasma concentration (Fig. 6). The phenomenon is called counterclockwise hysteresis or just hysteresis, provided that the model describes a stimulatory (positive) response. If the drug effect would be inhibitory (negative), the direction of the hysteresis would be clockwise. 

The rate at which an equilibrium concentration of a drug is reached in the extracellular fluid of a particular tissue will depend on the tissue s perfusion rate the greater the blood flow the more rapid the distribution of the drug from the plasma into the interstitial fluid. Thus, a drug will appear in the interstitial fluid of liver, kidney, and brain more rapidly than it will in muscle and skin (Table 3.2). The pharmacokinetic concept of volume of distribution (a derived parameter that relates the amount of drug in the body to the plasma concentration) is discussed more fully in Chapter 5. 

This section deals with the question of whether there are quantitatively detectable and interpretable correlations between the dose of an administered drug, or the concentration of a drug and its metabolites measured in the blood or plasma (blood or plasma level), and the therapeutic action or side effects observed. Investigations relating to questions of this type are called PK PD (pharmacokinetic pharmacodynamic) studies. The PK PD analysis is a bidirectional approach pharmacokinetics represent what the body does with a drug, and pharmacodynamics describes what a drug does to the body. The PK PD analyses are key elements of early drug development, and PK PD trials are able to answer specific disease-related efficacy and safety questions. 

Monitoring the effluent of a smoke stack, or the concentration of a drug in a patient requires that the sampling rate is as low as possible and that can be predicted with a known probability that between the sampling times no fatal concentration change will occur. If it is expected that the monitored value will exceed a preset value a simple action can prevent that administer some drug, open or close a value, etc. 

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