Dosage dose size

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... 

Dosage A composite term indicating the dose (size), its frequency, number of doses, and the duration of dosing. 

In this case, the co-solvent dosage rate is programmed in order to control the transient level of supersaturation in an effort to improve on the product crystal size distribution from simply dumping in all the solvent at the start of the batch. An experimental crystallizer within which a programmed microcomputer determines the set point of a variable speed-dosing pump is shown in Figure 7.7. Controlled co-solvent dosing improves the product crystal size, with a consequent increase in the filterability of the product. These process concepts are developed further in Chapter 9. 

In pharmaceutical and medical device development, clinical trials are classified into four main phases designated with Roman numerals 1,11, III and lY The various phases of development trials differ in purpose, length and number of subjects involved. Phase I trials are conducted to determine safe dose levels of a medication, treatment or product (National Institutes of Health, 2002). The main purpose is often to determine an acceptable single dosage - how much can be given without causing serious side-effects. Phase I trials will also involve studies of metabolism and bioavailabity (Pocock, 1983). The sample size of a Phase 1 clinical trial is usually small, ranging from 10-80 subjects (National Institutes of Health, 2002 Pocock, 1983). 

The course of post-LSD pupillary changes, with respect to dosage schedule and intensity and duration of effects, is a valuable tool. Pupil size 3 hr after the initial dose responded to the second dose of LSD and was an obvious measure to track in acute tolerance studies in humans. Given the number of rat studies in which this would be useful to monitor, the problem lies in determining rat mydriasis (easy in other animals) while a computerized pupillometer (developed by Martin Adler at Temple University) was informally tried by us once with LSD, systematic studies have not been done. 

With types D and C, twofold increments in dose are uniformly made throughout the whole dose range. This is in contrast to type E, in which the size of dosage increments over the dose range within subjects varies between 2- and 16-fold. Thus type E might be an unwise choice for a drug anticipated to have a narrow therapeutic index or a steep dose response. 

The maintenance dose may be defined as the size of the dose required to maintain the therapeutic range according to the dosage regimen. The maintenance dose needed to replace the amount lost over the dosing interval is the difference between the loading dose and the amount remaining at the end of the interval. It is calculated as,... 

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