Pharmacokinetics human equivalent dose

In order to extrapolate laboratory animal results to humans, an interspecies dose conversion must be performed. Animals such as rodents have different physical dimensions, rates of intake (ingestion or inhalation), and lifespans from humans, and therefore are expected to respond differently to a specified dose level of any chemical. Estimation of equivalent human doses is usually performed by scaling laboratory doses according to observable species differences. Unfortunately, detailed quantitative data on the comparative pharmacokinetics of animals and humans are nonexistent, so that scaling methods remain approximate. In carcinogenic risk extrapolation, it is commonly assumed that the rate of response for mammals is proportional to internal surface area... 

On the balance of the available evidence from human and animal studies presented in this chapter, it appears that CCM is well absorbed across a wide range of compositions and circumstances. For example, studies using isotopic and pharmacokinetic methods have shown that CCM is highly absorbable by both children and adults, in both tablet and beverage form, when consumed at levels ranging from an acute dose to chronic consumption (i.e., 200 mg Ca to 700 mg Ca/day, respectively), and for compositions covering a broad range of Ca citrate malate molar ratios that bracket the 6 2 3 neutral salt (i.e., molar ratios from 5 1 1 to 1.0 1.8 1.5 or the equivalent 6 10.8 9). 

Dose selection for subchronic and chronic toxicology studies should be based on the results from acute toxicity studies and pharmacokinetic evaluations. The three typical dose levels are (a) a no-toxic-effect level, which should be at least equivalent to, and hopefully a multiple of, the proposed human dose, (b) a dose level that produces a toxic effect in clinical observations, clinical pathology, or histopathologic changes, and (c) a dose level between these two. 

Biological monitoring (biomonitoring) Measnrement of a pesticide or its metabolites in the body fluids of exposed persons and conversion to an equivalent absorbed dose of the pesticide based on a knowledge of its human metabolism and pharmacokinetics (OECD, 1997). 

Becau.se oximes are quaternary ammonium compounds, they will be fully ionized in aqueous solution. Unless the accompanying anion ha.s pharmacological properties of its own, there would thius be no expectation that the PAM salts would differ in activity, if used on molar equivalent bases, cither qualitatively or quantitatively. Sidell etal. (1972b) compared the pharmacokinetics of 2-PAMCl and P2S after intravenous administration to human volunteers. The two PAM salts at the same (mass) dose (5 mg/kg) produced virtually identical plasma concentration-time curves. The... 

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