Individual dose

Since the dose is given to produce an effect, it is obvious that pharmacokinetics is a required but not yet sufficient tool for drug dose adjustment Pharmacokinetics (PK) must be combined with pharmacodynamics (PD) to derive the individualized dose. 

Drag => PK -I- PD => Individualized Dose Also pharmacogenetics (PG) can be integrated into a common concept, and be figured as pharmacokinetic (PK) and pharmacodynamic parameters (PD) for the individual patient. 

Based on therapeutic drag monitoring ( TDM) and the individual parameter estimates, every drag can be made applicable to every patient by individual dose adjustment. 

Responses to individual doses are given in those cases in which an LD50 could not be calculated. The LD50 for oral administration to rabbits was calculated using the method of Litchfield and Wilcoxon 9) the remaining values were calculated using the Weil modification of the method of Thompson 15). 

Collective dose—The sum of the individual doses received in a given period of time by a specified population from exposure to a specified source of radiation. Collective dose is expressed in units such as man-rem and person-sievert. 

Occluded applications Composition relatively invariant in use System size (area) predetermined Specific site prescribed for application Application technique highly reproducible Delivery is sustained Generally operate at unit drug activity, at least operate at steady activity Delivery is zero-order Serum levels related to product efficacy Bioequivalency based on pharmacokinetic (blood level) endpoint Unavoidable local tissue levels consequential only to system toxicity Individual dose interruptable Whole system removed when spent... 

Most capsules are filled on piston-tamp machines. These are fully automatic fillers in which pistons or tamping pins lightly compress the individual doses of powders into plugs (sometimes referred to as slugs ) and eject the plugs into the empty capsule bodies. The compression forces are low, often in the range of 50 200 N, or about 50-100-fold less than typical tablet compression forces. Hence, the plugs frequently will have the consistency of very soft compacts and will not be able to be recovered intact from the filled capsule. 

Ratain MJ, Mick R, Janish L et al. Individualized dosing of amonafide based on a pharmacodynamic model incorporating acetylator phenotype and gender. Pharmacogenetics 1996 6 93-101. 

Individual dose assessment requires radiological data on all external and internal sources contributing to occupational and non-occupational radiation exposure (Steinhausler and Pohl, 1983). This is of particular importance in the case of low level Rn-d exposure, as man is always exposed to Rn-d at varying levels through all stages of life, e.g. at school, home or work. The resulting lifetime risk from this chronic exposure is influenced by the latent... 

Variations in radiation doses to individuals within exposed populations also occur. Based upon previous exposures of people to Pu and Sr in fallout and exposures of laboratory animals to Ce, the dispersion of individual doses in a population is expected to be significant and should be considered in the formulation of population exposure guidelines. 

Blood pressure target Individual doses as needed B3... 

Subjective response plus rating scale Individual doses as needed Bl... 

Benzodiazepines Tremor, anxiety, diaphoresis, tachypnea, dyspho- Subjective response plus rating scale Individual doses as needed. Under- A2... 

Tromethamine, a highly alkaline solution, is a sodium-free organic amine that acts as a proton acceptor to prevent or correct acidosis. However, no evidence exists that tromethamine is beneficial or more efficacious than sodium bicarbonate. The usual empiric dosage for tromethamine is 1 to 5 mmol/kg administered IV over 1 hour and an individualized dose can be calculated as follows ... 

Rats were administered an intravenous dose of epinephrine of up to 12 //gleg after 30 min of exposure to the test compound monkeys and dogs were administered 8 Hg/kg (Mullin 1977) or 10 ji/g/kg (Hardy et al. 1989a) 5 min into the 10-min exposures. Dogs were administered individualized doses of epinephrine of 2 to 12 jig/kg (Hardy 1994). 

It was Friday, as I recall, when I came to work and found that the dmm had vanished. Thirty or forty pounds of chemically pure LSD had spent a week in my office and had now disappeared with no comment from anyone, no receipt form and no other paper work Enough LSD to intoxicate several hundred million people (by my estimate) had come and gone. I never received any explanation and never asked for one. I calculated, however, that if sold on the street in individual doses, the contents would have been worth close to a billion dollars ... 

Figures 1 and 2 show examples of the types of results obtained. In the spot test (Fig. 1), a small amount of the chemical to be tested is placed in the center of the dish, the chemical diffused out into the agar, and revertant colonies appear as a cloud around the central spot. This method is somewhat limited in sensitivity(3) but is extremely rapid. Normally, one tests individual dose levels of a chemical in the more sensitive plate test, and quantitative dose-response curves can be generated as shown in Figure 2. The initial portion of these curves is almost always linear, and most mutagens are detected at nanogram dose levels.

The theoretical line of additivity is the straight line that connects the individual doses of each of the single agents that produce a predetermined, hxed effect alone, for example an ED50 (50% response) of a given toxic or biochemical effect. 

Fig. 6.4 X -X are individual dose-response curves Y is the average dose-response curve for the population.

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