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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 4 of 4. This is the beginning of the thread.
Posted by Janelle on April 19, 2003, at 20:49:17
1. What is considered a short half-life, middle half-life and long half-life?
2. Is half-life dosage related, meaning if you're on a higher dose of a med, it will have a higher half-life (take longer to clear out of your system?) I think this is NOT the case, that the two are independent, but I cannot remember.
Thanks to whoever can answer these.
Posted by Paulie on April 20, 2003, at 12:56:16
In reply to HELP! Questions about med HALF-LIFE !, posted by Janelle on April 19, 2003, at 20:49:17
Hello Janelle,
Med half-life is independent of dosage. However, the greater the dosage the greater is the excretion from the body,usually in the form of metabolites. Hope this anwers your question.
Paul
Posted by Larry Hoover on April 20, 2003, at 13:31:11
In reply to HELP! Questions about med HALF-LIFE !, posted by Janelle on April 19, 2003, at 20:49:17
> 1. What is considered a short half-life, middle half-life and long half-life?
My thinking would put short half-life at less than 6 hours, and long at greater than 24 hours. The rest fall in the middle.
> 2. Is half-life dosage related, meaning if you're on a higher dose of a med, it will have a higher half-life (take longer to clear out of your system?) I think this is NOT the case, that the two are independent, but I cannot remember.
> Thanks to whoever can answer these.
The answer depends on the order of the reaction. Without getting into calculus (I don't think you want to go there, right?), there are three possible relationships.
1. A zero-order reactant is metabolized at a constant rate, regardless of the initial concentration. An example you're familiar with is alcohol. Typically, people metabolize alcohol at between one and one and half ounces per hour. The more you drink, the longer it takes.
2. A first order reaction proceeds independent of initial concentrations. By far, this is the most common sort we consider when we think of drugs and their half-lives. In this group, half-life is a fixed time (which varies between people, but is constant for each individual).
3. The third type is second order. It does depend on concentration, but in a bizarre way. The higher the initial concentration, the shorter the half life. Each subsequent half-life is twice as long as the one preceding it. I can't think of an example off the top of my head, but they do exist.
So, example two is probably the most relevant one to consider. In that example, dose has no effect on half-life.
Lar
Posted by medlib on April 20, 2003, at 16:36:16
In reply to HELP! Questions about med HALF-LIFE !, posted by Janelle on April 19, 2003, at 20:49:17
Hi Janelle--
Although a med's half-life is not affected by its initial concentration (dose amount times bioavailability), the level of med in your bloodstream at any given time *is* affected by initial dose amount.
Most medication is given in an amount and on a time schedule necessary to maintain a steady state concentration in the bloodstream within the med's therapeutic range. The therapeutic range of a drug is from the lowest dose which produces positive effects to the highest dose which doesn't produce toxic effects.
I'll use Seroquel, which has a 1/2 life of 6h and usually is given twice a day (bid), as an example. 6 hours after an initial dose of 200 mg.s, 100 mg.s would remain in the bloodstream. It might seem that if 1/2 is gone in 6h, all of it should be gone in 12h; but that is not the case. After 12 hours 50 mg.s remains (1/2 of the 1/2 left). At this point the second dose of 200 mg.s is taken (bid), making the blood concentration 250 mg.s. At the eighteenth hour the blood level is (roughly) 125 mg.s (1/2 of 250); and at 24 hours, it is 62.5 mg.s (1/2 of 125) and it is time for the next dose. In this manner, the blood level of Seroquel reaches a steady state in about 2 days. In actuality, it's not quite that simple, because one must consider the drug's time to peak concentration (Seroquel's is 1.5 hrs). I used Seroquel as an example because you had asked about it above and because its metabolites are not pharmacologically active (which would complicate calculations). Does this make any sense? If not, perhaps Larry will be willing to translate it into something more coherent.
Btw, Seroquel acts as an antihistamine, among other things; that may be what is making you sleepy. Some people adjust to it so that it's no longer soporific; but, as I tried to explain above, after a couple of days roughly the same level of Seroquel will be in your system at all times.
Hope this is of some help.---medlib
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