Dose to target

Adjustment based on body surface area signifies that the oral dose for children (mg/kg of body weight per day) is likely to be greater than for adults by a factor of two or so (Renwick, 1998). Such a body surface area-based dose adjustment should result in blood or tissue concentrations of parent chemicals that are comparable between children and adults, provided the toxicokinetic determinants are all related to body surface area. When this is not the 

The following section provides an overview of the functional and structural development of various organ systems as well as the molecular determinants associated with these processes. 

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Alpert HR (2008) Manipulation of free nicotine and its dosing to target high risk groups. Paper presented at the cigarette industry s entry into the smokeless tobacco market. Harvard School of Public Health, Boston, MA, July 10, 2008... 

Characteristics of the radiation exposure itself a. magnitude of dose to target organ or tissue... 

The presence of air pollutants in the surrounding ambient air is only one aspect of determining the impact on human beings. An air pollution instrument can measure the ambient concentration of a pollutant gas, which may or may not be related to its interaction with individuals. More detailed information about where and for how long we are breathing an air pollutant provides additional informahon about our actual exposure. Finally, how an air pollutant interacts with the human body provides the most useful information about the dose to a target organ or bodily system. 

The calculated peak concentration is not always the measured concentration. For bi-exponential kinetics the calculated peak concentration is less, but after oral dosing, the calculated peak concentration is higher than the highest measurable plasma concentration. The peak concentration provides a target for the loading dose to start with (Dload). 

CF patients have a larger volume of distribution and enhanced total body clearance of many antibiotics, which often results in the need for higher doses to attain target levels. 

FIGURE 27-3. Serum concentrations of carbamazepine in the presence and absence of appropriate dose titration. Carbamazepine induces its own metabolism, so maintenance dose requirements are much greater than starting doses. To avoid excessive adverse effects, starting doses should be 25% to 30% of the target maintenance doses and increased gradually to the target maintenance dose, usually over 3 to 4 weeks. 

Titrate dosage to target over 3-4 weeks Adults 1 0-20 mg/kg per day as a divided dose Children 20-30 mg/kg per day as a divided dose Loading dose ... 

Obtain the first follow-up serum uric acid level within 6 months of starting therapy. Then monitor levels at least every 6 to 12 months, and adjust the dose to achieve a target serum uric acid level of less than 6 mg/dL (less than 357 pmol/L). 

The conventional concentration of benzalkonium chloride in eyedrops is 0.01%, with a range of 0.004-0.02% [111]. While uptake of benzalkonium chloride itself into ocular tissues is limited [113], even lower concentrations of benzalkonium chloride have been reported to enhance corneal penetration of other compounds including therapeutic agents [93,112,114]. The differential effect of this preservative on the cornea compared to the conjunctiva can be exploited to target a drug for corneal absorption and delivery to the posterior segment of the eye [115]. Its use has been proposed as a means of delivering systemic doses by an ocular route of administration [116]. 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism s ability to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or other characteristic or a preexisting disease that results in an increase in absorbed dose, biologically effective dose, or target tissue response. If biomarkers of susceptibility exist, they are discussed in Section 2.9, Populations That Are Unusually Susceptible. 

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