Factors, pharmacokinetic

Currently, all marketed verapamil products are racemic mixtures of R and S enantiomers (7,8). The totd pharmacological activity of a verapamil dose is determined by the combined bioavailability of both individual enantiomers. The S enantiomer is preferentially metabolized after oral dosing, resulting in the R enantiomer being the more prevalent in the systemic circulation (8). The actual value of the enantiomeric ratio (R S) in the plasma, however, is determined by a combination of factors. Pharmacokinetic distinctions between the two enantiomers (e.g., volumes of... 

Dittrich E, Thoenen H, Sendtner M (1994) Ciliary neurotrophic factor Pharmacokinetics and acute-phase response in the rat. Ann Neurol 35 151-163. 

Pharmacokinetics is the study of how the body affects an adiriinistered dmg. It measures the kinetic relationships between the absorption, distribution, metaboHsm, and excretion of a dmg. To be a safe and effective dmg product, the dmg must reach the desired site of therapeutic activity and exist there for the desired time period in the concentration needed to achieve the desired effect. Too Htde of the dmg at such sites yields no positive effect ( MTC) leads to toxicity (see Fig. 1). For intravenous adininistration there is no absorption factor. Total body elimination includes both metabohc processing and excretion. 

Pharmacodynamics is the study of dmg action primarily in terms of dmg stmcture, site of action, and the biochemical and physiological consequences of the dmg action. The availabiUty of a dmg at its site of action is deterrnined by several processes (Fig. 1), including absorption, metaboHsm, distribution, and excretion. These processes constitute the pharmacokinetic aspects of dmg action. The onset, intensity, and duration of dmg action are deterrnined by these factors as well as by the avadabihty of the dmg at its receptor site(s) and the events initiated by receptor activation (see Drug delivery). 

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). 

One approach to combating antibiotic resistance caused by P-lactamase is to inhibit the enzyme (see Enzyme inhibition). Effective combinations of enzyme inhibitors with P-lactam antibiotics such as penicillins or cephalosporins, result in a synergistic response, lowering the minimal inhibitory concentration (MIC) by a factor of four or more for each component. However, inhibition of P-lactamases alone is not sufficient. Pharmacokinetics, stability, ability to penetrate bacteria, cost, and other factors are also important in determining whether an inhibitor is suitable for therapeutic use. Almost any class of P-lactam is capable of producing P-lactamase inhibitors. Several reviews have been pubUshed on P-lactamase inhibitors, detection, and properties (8—15). 

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. 

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.

Bolt HM. 1987. Pharmacokinetic factors and their implication in the induction of mouse liver tumors by halogenated hydrocarbons. Arch Toxicol Suppl 10 190-203. 

Sato A, Endoh K, Kaneko T, et al. 1991. A simulation study of physiological factors affecting pharmacokinetic behavior of organic solvent vapours. Br J Ind Med 48 342-347. 

The identification of a drug requires optimization of the balance among multiple properties, among them potency/efficacy, pharmacokinetics (PK), safety, and intellectual property. As a consequence, these are also the factors that are important to... 

As the number of medications that a patient takes increases, so does the potential for DDIs. Disease severity, patient age, and organ dysfunction are all risk factors for increased DDIs. In general, DDIs can be broken down into two categories (1) pharmacokinetic interactions and (2) pharmacodynamic interactions. 

Cetuximab is a human/mouse antibody that binds to the epidermal growth factor receptor to block its stimulation. The pharmacokinetics of cetuximab demonstrate a volume of distribution that approximates the vascular space and a terminal half-life of 70 to 100 hours. Cetuximab has shown clinical activity in the treatment of colorectal cancer. An acnelike rash may appear on the face and upper torso 1 to 3 weeks after the start of therapy. Other side effects include hypersensitivity reactions, interstitial lung disease, fever, malaise, diarrhea, abdominal pain, and nausea and vomiting. 

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