Dose calculations converting

Doses calculated in animals are converted to equivalent doses in humans on the basis of comparative physiological considerations (c.g., ventilatory parameters and regional lung surface areas). Additionally, if the e.xposure period was discontinuous, it is adjusted to reflect continuous e.xposure. 

Statistical Treatment of Data. Each dose ratio point was the mean of three determinations. SrTly points between 20 and 80% on the dose response curves were utilized for the calculation of the dose ratio. After the dose was converted to a log value and the response to percent of the maximum, a best fit line was determined by linear regression. 

One further point which should be considered is the importance of dose size. Because of the (R) — (S) conversion, the dosage of the (S) form administered may be as much as two or three times the anticipated dose. One can visualize an elderly 90 lb lady, with decreased renal function, who is administered a racemic drug. She receives the normal dose calculated for a 150 lb person (because of the way the tablets are made up). Because of decreased renal function and increased retention there is time for all the (i ) enantiomer to be converted to the (S) enantiomer. Effectively, she will receive three times the needed dose of the active drug and the area under the dose—time curve will be much greater. It is hardly surprising that adverse side effects sometimes occur.99... 

The inhalation RfD is derived from the NOAEL by applying uncertainty factors similar to those listed above for oral RfDs. A UF of 10 is used when e.Ktrapolating from animals to humans in addition to the calculation of the human equivalent dose, to account for interspecific variability in sensitivity to the to. icant. The resulting RfD value for inhalation c. posure is generally reported as a concentration in air in mg/m for continuous, 24 hour/day c. posurc, although it may be reported as a corresponding inhaled intake (in mg/kg-day). A human body weight of 70 kg and an inhalation rate of 20 nv /day are used to convert between an inhaled intake e.xprcsscd in units of mg/kg-day and a concentration in air e. pressed in mg/m. ... 

Dosage calculations when converting from morphine to methadone are not linear. The equianalgesic dose of methadone will decrease progressively as the morphine equivalents increase (Table 30-4). 

MeV. WL-R = 100% x WL/radon concentrations (pCi/1). The dose conversion factor of 0.7 rad/working level month (WLM) (Harley and Pasternack, 1982) was used to calculate the mean absorbed dose to the epithelial cells and a quality factor (OF) of 20 was applied to convert the absorbed dose to dose equivalent rate. For example, from the average value of (WL) obtained from the arithmetic mean radon concentrations measured in the living area during winter and summer in South Carolina (Table I), the calculated dose equivalent rate is 4.1 rem/yr, e.g.,... 

Convert the NOAEL to the human equivalent dose (HED) using the data from Table 5.3 (calculations are based on body surface areas). 

For continuous data, there are still a number of outstanding issues regarding the benchmark including (Crump 2002) (1) definition of an adverse effect (2) whether to calculate the BMD from a continuous health outcome, or first convert the continuous response to a binary (yes/no) response (3) quantitative definition of the BMD, in particular in such a manner that BMD from continuous and binary data are commensurate (4) selection of a mathematical dose-response model for calculating a BMD (5) selection of the level of risk to which the BMD corresponds and (6) selection of a statistical methodology for implementing the calculation. 

When converting from Avinza or Kadian to parenteral opioids, it is best to calculate an equivalent parenteral dose and then initiate treatment at half of this calculated value. As an example, an estimated total 24-hour parenteral morphine requirement of a patient receiving Avinza or Kadian is one-third of the dose of Avinza or Kadian. This estimated dose should then be divided in half, and this last calculated dose is the total daily dose. This value should be further divided by 6 if the desire is to dose with parenteral morphine every 4 hours. 

The ERA has calculated a subchronic oral reference dose (RfD) of 7x10 mg/kg/day for carblon tetrachloride based on a NOAEL of 1 mg/kg/day (converted to 0.71 mg/kg/day based on intermittent exposure) for rats in a 12-week study (Bruckner et al. 1986 ERA 1989b IRIS 1993). The critical effect was liver toxicity. A chronic oral RfD of 7x10 mg/kg/day was also calculated based on the same NOAEL used for the subchronic RfD. The ATSDR has calculated an acute inhalation MRL of 0.2 ppm based on a LOAEL of 50 ppm for liver effects in an acute 4-day rat inhalation study (David et al. 1981), and an intermediate inhalation MRL of 0.05 ppm based on a NOAEL of 5 ppm for liver effects in an intermediate-duration (187-192 days) inhalation study in rats (Adams et al. 1952). The ATSDR has also calculated an acute oral MRL of 0.02 mg/kg/day based on a LOAEL of 5 mg/kg/day over 10 days for liver effects in the rat (Smialowicz et al. 1991), and an intermediate oral MRL of 0.007 mg/kg/day based on a NOAEL of 1 mg/kg/day over 12 weeks (converted to 0.71 mg/kg/day based on intermittent exposure) for liver effects in the rat (Bruckner et al. 1986). 

A dosimeter suitable for measuring the radiation intensity at doses in the range of 10 to 8 X 1CP rads consists of a solution of 0.001 M ferrous sulfate-0.01M cupric sulfate in 0.0ION sulfuric add. If the recommended concentrations are used, the dosimeter is reproducible to 0.3% and stable after irradiation to approximately 2% per week. The dose received by the recommended dosimeter can be calculated, if read at 25°C., by converting the change in absorbance (AA) using the equation dose (rads) =... 

If it is known, for example, that the following product, product B, will have a maximum daily dose of 500 mg (e.g., 10 tablets, each containing 50 mg of active) and a batch size of 300 kg of active ingredient, then it is possible to calculate a total carryover limit as follows. Converting the 300-kg batch to mg yields... 

Case Example Pharmacokinetic Calculations to Interpret Phthalate Urinary Biomarker Data. The previous descriptions focused on blood or adipose biomarker concentrations that were converted to body burden to yield estimates of daily dose based on chemical half-life. A modified form of that is conversion of urinary biomarker data to daily exposure dose via simple model calculations as described for phthalates. 

The widespread detection of phthalate metabolites in human urine has produced questions about public-health risks, especially with regard to antiandrogen effects that can influence male gonadal development (Gray et al. 2000 Parks et al. 2000). The extrapolation from urinary biomonitoring results to exposure and risk assessment has been facilitated by calculations that convert urinary metabolite concentrations to intake dose of the parent phthalate (Koo et al. 2002 Koch et al. 2003 Kohn et al. 2000 David 2000). The parent diester phthalates are rapidly and completely metabolized to the monoester metabolites, which are rapidly cleared by the kidney. Those features allow one to assume that the daily excretion rate of metabolite is equal to the daily intake rate of the parent chemical. Furthermore,... 

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