Duration of drug

Fhtients with kidney disease may exhibit drug toxicity and a longer duration of drug action. The dosage of drugp may be reduced to prevent the accumulation of toxic levels in the blood or further injury to the kidney. 

FIGURE 10 Effect of thickness on duration of drug release frona pol5nner discs prepared from 3,9-bis(ethylidene-2,4,8,10-tetraoxaspiro-[5,5]undecane) and a 50 50 mole ratio of trans-cyclohexane dimethanol and 1,6-hexanediol at pH 7.4 and 37°C. Polymer contains 4 wt% drug and 0.2 wt% poly(sebasic anhydride). (From Ref. 20.)... 

The single-dose toxicity studies were performed in two mammalian species, rat and mouse, by the route used in clinical practice, that is oral, as well as that ensuring adequate systemic exposure to the drug, that is intravenous. The subacute (3 months) toxicity studies were correctly carried out in the two animal species (rat, dog) in which also the pharmacokinetics was studied. Since in accordance with the International Conference on Harmonization (CPMP/ICH/286/95), 3-month toxicity studies support clinical trials for up to 1 month s duration (the longest duration of drug administration in clinical use), chronic toxicity studies have not been performed. 

Early Measurement of Drug Activity. Preliminary studies of activity or potential therapeutic benefit may be conducted in Phase I as a secondary objective. Such studies are generally performed in later phases but may be appropriate when drug activity is readily measurable with a short duration of drug exposure in patients at this early stage. Frequently such evaluations are done in what are called Phase lb studies. 

Although there is not a recognized definition for the term context , it is used to identify the fact that the half time will usually alter in the setting of varying durations of drug infusion. 

Using BrdU pulse labelling was evident that at equivalent Gfio, compounds produced a delay in the S phase followed by an accumulation in G2/M, as is expected for mechanism of action of topi inhibitor. Antiproliferative activities was also found after shorter treatments as previously reported, when the duration of drug treatment was limited to 1 hour (Figure 6), at doses from 30 to 300 nM. 

A. Importance of protein binding for intensity and duration of drug effect... 

Despite the fact that the present classifications are extremely convenient for practical medical personnel, it should be kept in mind that the duration of drug action—especially of the first three groups of compounds—depends on various factors besides the structure of the compounds, such as drug form, method of administration, pathology for which the drug is being used, general treatment time, etc. 

Excretion, along with metabolism and tissue redistribution, is important in determining both the duration of drug action and the rate of drug elimination. Excretion is a process whereby drugs are transferred from the internal to the external environment, and the principal organs involved in this activity are the kidneys, lungs, biliary system, and intestines. 

Benzodiazepines are ciassified as short, medium, and iong acting. This reiates to the duration of drug action in the body. Length of action can aiso be infiuenced by the heaith of the patient s iiver and the patient s age and weight. ... 

A number of SSRIs and SNRIs were tested for their effects on cognitive function in repeated-dose studies in healthy, non-depressed volunteers. Studies with SSRIs before 1999 have been reviewed by Lane and O Hanlon (1999) and some more recent reports deal with nefazodone. paroxetine and sertraline (Furlan et al., 2001 Schmitt et al., 2001 van Laar et al.. 2002). However, considering the populations studied in these trials (non-depressed subjects), the duration of drug administration (1 2 weeks) and the mostly low drug doses used, the relevance of these studies for a clinical situation may be questioned. 

Problems of optimal dosage and duration of drug treatment for mental disorders have also been addressed in numerous controlled studies and are presented separately below for antipsychotics, antidepressants, mood stabilizers, anxiolytics and psychostimulants. This division again makes sense because the disorders treated and the therapeutic approaches used differ in significant aspects and the empirical studies carried out in the individual indications show major qualitative and quantitative differences. 

Bioavailability, after determining the rate and amount of drug absorbed, and the duration of drug s presence in the body fluid gives an idea about the therapeutic efficiency and toxicity. 

Appropriate sleep hygiene techniques should always be considered and, when possible, used in lieu of pharmacotherapy. When medication is given, such nonpharmacological approaches may significantly decrease the amount and duration of drug exposure. Sleep therapies include the following ... 

There are several reasons for different routes of administration used in clinical medicine (Table 3-3)—for convenience (eg, oral), to maximize concentration at the site of action and minimize it elsewhere (eg, topical), to prolong the duration of drug absorption (eg, transdermal), or to avoid the first-pass effect. 

For a patient in severe pain, the administration of an opioid analgesic is usually considered a primary part of the overall management plan. Determining the route of administration (oral, parenteral, neuraxial), duration of drug action, ceiling effect (maximal intrinsic activity), duration of therapy, potential for adverse effects, and the patient s past experience with opioids all should be addressed. One of the principal errors made by physicians in this setting is failure to adequately assess a patient s pain and to match its severity with an appropriate level of therapy. Just as important is the principle that following delivery of the therapeutic plan, its effectiveness must be reevaluated and the plan modified, if necessary, if the response was excessive or inadequate. 

Remmer H. In Brodie BB, Erdos EG, eds. Metabolic Factors Controlling Duration of Drug Action, Proceedings of First International Pharmacological Meeting, Vol. 6. New York Macmillan, 1962. 

Pharmacokinetics is defined as the study of the quantitative relationship between administered doses of a drug and the observed plasma/blood or tissue concentrations. The field of pharmacokinetics is concerned with drug absorption, distribution, biotransformation, and excretion or elimination. These processes, in addition to the dose, determine the concentration of drug at the effector or active site and, therefore, the intensity and duration of drug effect. 

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