Calculating, desired dose

A single bolus dose administration of 50 mg of a drug showed the following pharmacokinetic parameters C0 = 2.5 mg/mL, and tm = 5.5 hours. If the desired minimum steady-state concentration is 2 mg/mL, calculate the dose that should be administered every six hours, and the expected maximum steady-state concentration with the new dose. 

The desired dose of dialysis in terms of solute removal can be expressed as a urea reduction ratio (URR) or the Kt/V (pronounced K-T-over-V ). The URR is calculated as ... 

There are two methods that are used to calculate a dose. These are the formula method and the ratio-proportion method. Both use the on hand dose of a medication to determine the desired dose based on the medication prescription. 

Theophylline is relatively insoluble in an aqueous vehicle and, so, there is a practical difficulty in the administration of theophylline in that form. Therefore, aminophylline, which is the water-soluble salt (salt value of 0.8 to 0.85) of theophylline, is used. In this example, the salt value suggests that 100 mg aminophylline will provide 80-85 mg of theophylline. In other words, if the calculated loading dose required for attaining the desired theophylline plasma concentration instantaneously is 80 mg, then 100 mg of aminophylline must be administered. Failure to take into consideration the salt value, in this example, will result in 20% error. 

Using this dosing interval, and rearranging the equation in Step 3, calculate the dose (Xq) needed to attain the desired "average" steady-state concentration. 

It may take a long time and the administration of many doses (over seven or eight) before the desired "average" steady-state drug concentration is attained. Therefore, an intravenous bolus loading dose (DJ may be administered to obtain an instant steady-state condition. The calculated loading dose should be such that that, at time t after its administration, the plasma concentration of drug is the desired minimum plasma concentration at steady state, that is ... 

Assuming TheraSphere microspheres distribute in a uniform manner throughout the liver and undergoes complete decay in situ, radioactivity required to deliver the desired dose to the liver can be calculated using the following formula [15] ... 

The goal of pharmacokinetics is the quantitative description of drug entry, distribution, and elimination in the body. These processes are typically integrated into a mathematical model which uses a system of equations such as Eqs. (l)-(20) to calculate the systemic concentration due to a certain dose administered to the patient. If the pharmacodynamic characteristics of the drug can be clearly defined, the desired concentration at the target or in the plasma can be specified, and the pharmacokinetic model can be used to calculate the dose to attain the effective concentration. 

Acute toxicity studies are often dominated by consideration of lethaUty, including calculation of the median lethal dose. By routes other than inhalation, this is expressed as the LD q with 95% confidence limits. For inhalation experiments, it is convenient to calculate the atmospheric concentration of test material producing a 50% mortaUty over a specified period of time, usually 4 h ie, the 4-h LC q. It is desirable to know the nature, time to onset, dose—related severity, and reversibiUty of sublethal toxic effects. 

The reader should note tliat since many risk assessments have been conducted on the basis of fatal effects, there are also uncertainties on precisely what constitutes a fatal dose of thennal radiation, blast effect, or a toxic chemical. Where it is desired to estimate injuries as well as fatalities, tlie consequence calculation can be repeated using lower intensities of exposure leading to injury rather titan dcatli. In addition, if the adverse healtli effect (e.g. associated with a chemical release) is delayed, the cause may not be obvious. Tliis applies to both chronic and acute emissions and exposures. 

Several aspects of the problem of herbicides being contaminated with nitrosamines, and the resulting inadvertent introduction of nitrosamines into the environment, will be discussed in other papers in this symposium. Unrecognized until less than five years ago, the situation has inspired intense debate and prompted several of the environmental chemistry studies mentioned in this paper. Like the presumed threat from the in vivo nitros-ation of pesticide residues, discussions sometimes lack the type of anticipated dose and effect calculations just mentioned. Unlike the active ingredients, whose benefits can justify residue tolerances and acceptable daily intakes, nitrosamine contaminents afford no known benefits, and the desirability of minimizing their levels is undisputed. 

Calculate an appropriate factor-concentrate dose for a product, given the percentage correction desired. 

A loading dose that produces a of 35 pg/mL is desired, and this can be calculated as follows [from Eq. (16)] ... 

If VD is significantly altered or a specific concentration is desired, estimation of a dosage regimen becomes more complex. The dosing interval (Tf) is calculated as ... 

Intravenous bolus dose of a 500-mg dose of an antibiotic every six hours in a patient produces minimum steady-state concentration of 10 meg/ mL. If the desired minimum steady-state concentration in this patient is 16 mcg/mL, calculate the size of dose needed to change this concentration. Assume that the drug follows linear kinetics. 

Once the clearance rate for a drug is known, the frequency of dosing may be calculated. It is usually desirable to maintain drug concentrations at a steady-state level within a known therapeutic range. This will be achieved when the rate of drug administration equals the total rate of clearance. 

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 principle that emerges from these three examples is a simple one. The only factors important in calculating an intravenous loading dose of a drug are the desired plasma concentration and the apparent volume of distribution. Other kinetic parameters do not come into this very straightforward calculation. 

The quantal dose-response curve represents estimates of the frequency with which each dose elicits the desired response in the population. In addition to this information, it also would be useful to have some way to express the average sensitivity of the entire population to phenobarbital. This is done through the calculation of an ED50 (effective dose, 50% i.e., the dose that would protect 50% of the animals). This value can be obtained from the dose-response curve in Figure 22A, as shown by the broken lines. The ED50 for phenobarbital in this population is approximately 4mg/kg. 

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