Pharmacodynamics and Pharmacokinetics

Pharmacology may be described as the study of the properties of drugs and how they interact with/affect the body. Within this broad discipline exist (somewhat artificial) subdisciplines, including pharmacokinetics and pharmacodynamics. 

Pharmacokinetics relates to the fate of a drug in the body, particularly its ADME, i.e. its absorption into the body, its distribution within the body, its metabolism by the body, and its excretion from the body. 

The emphasis at this stage of the drug development process is upon assessing safety. Satisfactory pharmacological, and particularly toxicological, results must be obtained before any regulatory authority will permit commencement of human trials 

Pharmacokinetic profile Pharmacodynamic profile Bioequivalence and bioavailability Acute toxicity Chronic toxicity 

The results of such studies not only help to identify any toxic effects, but also point to the most appropriate method of drug administration, as well as the most likely effective dosage regime to employ. Generally, ADME studies are undertaken in two species, usually rats and dogs, and studies are repeated at various different dosage levels. All studies are undertaken in both males and females. 

Pharmacokinetics relates to the fate of a drug in the body, particularly its ADME, i.e.  

If initial clinical trials reveal differences in human versus animal model pharmacokinetic profiles, additional pharmacokinetic studies may be necessary using primates. 

Pharmacokinetic and pharmacodynamic considerations have been discussed several times in the book. It was noted in the Preface that there would be a certain degree of planned repetition in the book Concepts are introduced at one point and then integrated with other material at a later point. This has been true for pharmacokinetics and pharmacodynamics. It is also true for some of the genetic discussions that follow in this chapter. 

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Geriatric factors a variety of factors, both pharmacokinetic and pharmacodynamic, that contribute to variable dmg responses in the elderly. These responses are not seen for every class of dmg. Thus, the depressant effects of the glycosides also appear to increase with aging (116,117). 

V. I. Avramis, in A Clinician s Guide to Chemotherapy, Pharmacokinetics and Pharmacodynamics,... 

Pharmacokinetic and Pharmacodynamic Aspects of Drug Development of Agents for... 

Osborn BL, Olsen HS, NardeUi B, Murray JH, Zhou JX, Garcia A, Moody G, Zaritskaya LS, Sung C (2002) Pharmacokinetic and pharmacodynamic studies of a human serum albumin-interferon-alpha fusion protein in cynomolgus monkeys. J Pharmacol Exp Ther 303 540-548 Ozes ON, Reiter Z, Klein S, Blatt LM, Taylor MW (1992) A comparison of interferon-Conl with natural recombinant interferons-alpha antiviral, antiproliferative, and natural kiUer-inducing activities. J Interferon Res 12 55-59... 

BEIs apply to 8 hr exposures, five days a week. However, BEIs for altered working schedules can be extrapolated on pharmacokinetic and pharmacodynamic bases. BEIs should not be applied, either directly or through a conversion factor, to the determination of safe levels for non-occupational exposure to air and water pollutants, or food contaminants. The BEIs are not intended for use as a measure of adverse effects or for diagnosis of occupational illness. 

COMPUTER SIMULATIONS IN PHARMACOKINETICS AND PHARMACODYNAMICS REDISCOVERING SYSTEMS PHYSIOLOGY IN THE 21ST CENTURY... 

Figure 21.2 The exposure-response road map passes through pharmacokinetics and pharmacodynamics. This sequence of events is essentially the same as that which informs compnter simulation of clinical trials, with the addition of complicating, bnt important, factors snch as protocol adherence and dropouts.

Pharmacokinetic and Pharmacodynamic Resources, http //www.boomer.org/ pkin/ (accessed October 1, 2005)... 

Gabrielsson J and Weine, D. Pharmacokinetic and pharmacodynamic data analysis concept and applications, 3rd Edition. Stockholm Swedish Pharmaceutical Society, 2000. 

The consequence of moving consciously toward this model will be the provision of a robust and scalable IT infrastructure and systems able to cope with exponentially growing data mountains that will need to be integrated and shared, accessed and mined in the most effective way. It will also require formidable computing power and sophisticated algorithms to be able to simulate both organs and whole body systems to reduce expensive failures in the clinic and predict much earlier the pharmacokinetic and pharmacodynamic properties and toxicological and efficacy profiles of molecules in pharmaceu-... 

Become familiar with the pharmacokinetic and pharmacodynamic principles of medications prescribed in ICU patients... 

Design a diuretic regimen that considers the pharmacokinetic and pharmacodynamic... 

As the disease progresses, most patients develop response fluctuations. Treatment is based on optimizing the pharmacokinetic and pharmacodynamic properties of Parkinson s disease medications. 

Assess appropriate selection of these medications for pharmacokinetic and pharmacodynamic DDIs (Table 52-6), need (e.g., do renal transplant recipients need to continue to take erythropoietin ), and efficacy. 

Drug-specific considerations in antimicrobial selection include the spectrum of activity, effects on nontargeted microbial flora, appropriate dose, pharmacokinetic and pharmacodynamic properties, adverse-effect and drug-interaction profile, and cost. 

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