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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 73. This is the beginning of the thread.
Posted by Janelle on April 4, 2002, at 18:11:03
Thanks!
Posted by fachad on April 4, 2002, at 21:01:57
In reply to Could someone explain HALF-LIFE w/ example!, posted by Janelle on April 4, 2002, at 18:11:03
Ok, Janelle, here's my attempt:
Half-life is the time it takes for the concentration of a drug in your system to drop by 50%.
Here's a simple example. Suppose you have a concentration of 100mg/l (100 milligrams of drug per liter of blood) at say 1 PM, and the drug has a half-life of 2 hours. If you had blood drawn and tested every 2 hrs it would look like this:
1PM 100 mg/l
3PM 50 mg/l
5PM 25 mg/l
7PM 12.5 mg/lNotice that in the first 2 hours, between 1PM and 3PM, your body got rid of 50mg/l of the drug.
But then in the same amount of time, the 2 hours between 3PM and 5PM, your body only got rid of 25 mg/l.
But in all cases, your body gets rid of half of the however much of the drug is there in the 2 hour interval. That is why it is said to have a 2-hour half-life.
The explanation for this is that the rate at which you body breaks down drugs (well, those with linear pharmacokinetics, anyway) is relative to the concentration of the drug in your system, not an absolute rate of elimination. (It get’s rid of 50% per 2 hours, not a fixed amount per 2 hours)
This is really significant because drugs with short half-lives will wear off quickly. This could be a good thing, like a sleeping pill that doesn't make you groggy the next day. But it could be bad if your symptoms break thru.
Also, if the half-life is short and you want to keep the concentrations in your system steady, you have to take the drug every half-life.
So if you want steady concentrations of a drug with a 24-hour half-life, you can take it once a day. If you want steady concentrations of a drug with an 8 hr half-life, you need to take it 3 times a day.
The problem with drugs with really long half-lives is that the build up in your system and can get to really high concentrations, even if you are only taking them once per day.
Prozac can still be in your system 6 weeks after you take the last dose.
Posted by Janelle on April 4, 2002, at 21:14:08
In reply to Half-Life: Explained with Examples and Importance » Janelle, posted by fachad on April 4, 2002, at 21:01:57
Believe it or not, I followed everything you said (I should say that I went into it knowing that a half life is how long it takes your body to eliminate half the drug), but could you carry your example further and show when the drug would be completely GONE from the body - that is the part I don't quite get! Thanks!
Posted by Sunnely on April 4, 2002, at 21:52:58
In reply to Could someone explain HALF-LIFE w/ example!, posted by Janelle on April 4, 2002, at 18:11:03
(Elimination) Half-life (t1/2) is the time during which half or 50% of an amount of drug is cleared from the body, usually expressed in hours. As a rule, once in steady-state level, it takes approximately 4-5 half-lives to eliminate a drug from the body. For example, a drug with a half-life of 24 hours will take 5 days to be eliminated from the body.
The t1/2 determines the rate at which a drug accumulates in the body tissues; drugs with longer half-lives accumulate more gradually to steady state concentration (Css). In addition, drugs with long half-lives disappear from the body more gradually following discontinuation, whereas those with shorter half-lives are eliminated more rapidly (which for some drugs can result in the rapid appearance of an intense withdrawal syndrome). The t1/2 can also guide a physician in choosing the frequency of dosing intervals; drugs whose half-lives exceed 24 hours usually can be administered once a day.
Some examples:
1. Long t1/2 drug - Prozac:
Fluoxetine (parent compound) with half-life of 3-5 DAYS; norfluoxetine (ACTIVE metabolite or daughter compound) with a half-life of 7-15 DAYS.At repeated administration, it will take approximately 5-8 weeks for Prozac to reach a steady state concentration (Css): 7-15 days x 5 (half-lives) = 5-8 weeks. When Prozac is stopped, it will take approximately same amount of time to eliminate the drug from the body, provided all other factors remain constant.
2. Short t1/2 drug - Paxil
Paroxetine has a t1/2 of 24 HOURS. It has no active metabolite.At repeated administration, it will take approximately 5 days to reach Css: 24 hours x 5 (half-lives) = 5 days. When stopped, it will take approximately the same amount of time to eliminate the drug from the body, provided all other factors remain constant.
One advantage of having long t1/2: It is opined that the presence of an active metabolite and half-life are the reasons that withdrawal symptoms with Prozac is uncommon. OTOH, the absence of an active metabolite and shorter half-life can lead to more rapid and distressing withdrawal symptoms with Paxil (also Effexor). Likewise, benzodiazepines with shorter half-lives tend to have more rapid occurrence and severe withdrawal symptoms than longer half-lives.
One disadvantage of having long t1/2: If an adverse reaction occurs, it takes longer time to dissipate. May be a major concern if the reaction is life-threatening.
Half-life can change with certain factors such as age, genetic polymorphism (deficiency in cytochrome genes), gender, concurrent meds/herbs/beverages taken, concomitant medical illness (e.g., liver, kidney, heart, infection, etc.), smoking habits, alcohol consumption.
Steady state blood concentration (Css) is the point at which the tissue concentration of a drug becomes stable (i.e., when the amount of the drug eliminated every 24 hours is equal to the amount administered every 24 hours, provided everything else remains constant). Css is usually considered the level at which the drug is most effective.
One major factor that affects t1/2 and Css is drug-drug interaction. For example, adding Prozac or Paxil to desipramine may lead to increased desipramine blood level and subsequent increase in anticholinergic side effects and even heart-related side effects. Adding Prozac or Paxil to codeine or tramadol (Ultram) may lead to loss of their pain-killing effects as they are prevented from being converted into more active metabolites.
Adding carbamazepine (Tegretol) to birth control pills may decrease the blood level of the birth control pills leading to loss of its contraceptive effect, in turn leading to unwanted pregnancy. Similar reaction can happen if St. John's wort is taken with birth control pills.
Taking alprazolam (Xanax), triazolam (Halcion), or zolpidem (Ambien) with nefazodone (Serzone) may increase their side effects. Similar drug-drug interaction can happen when taking grapefruit juice with these meds.
Chronic smoking can lower the blood level of Zyprexa and Clozaril which could lead to loss of effectiveness.
> Thanks!
Posted by Janelle on April 4, 2002, at 22:00:45
In reply to Re: Could someone explain HALF-LIFE w/ example! » Janelle, posted by Sunnely on April 4, 2002, at 21:52:58
Posted by Janelle on April 4, 2002, at 22:01:43
In reply to Sunnely: wow, thanks, how do you know this stuff?! (nm) » Sunnely, posted by Janelle on April 4, 2002, at 22:00:45
Posted by fachad on April 4, 2002, at 22:04:53
In reply to FACHAD:Thanks, great stuff, one teeny question: » fachad, posted by Janelle on April 4, 2002, at 21:14:08
I think after 5 half lives have elapsed without any more doses the drug is considered effectively gone.
> Believe it or not, I followed everything you said (I should say that I went into it knowing that a half life is how long it takes your body to eliminate half the drug), but could you carry your example further and show when the drug would be completely GONE from the body - that is the part I don't quite get! Thanks!
Posted by Janelle on April 4, 2002, at 22:58:48
In reply to Re: FACHAD:Thanks, great stuff, one teeny question: » Janelle, posted by fachad on April 4, 2002, at 22:04:53
Is there a relationship between how long it takes a drug to start working (e.g. 2 hours after being taken) and that drug's half life?
Meaning do drugs that take less time to start working also have shorter half-lives?
Posted by Janelle on April 4, 2002, at 23:50:20
Hi there!
1) I'm afraid because I typed it all in caps and there is another thread right below it all in caps that my other question regarding half-lives might get missed, so could you please go back up to the HALF-LIFE thread I started and answer the question that begins with "RELATIONSHIP BETWEEN" ... you could answer it up there, that would be great, thanks!
2) Please humor me and bear with me a bit more here cuz I'm still not getting the whole story with this half-life stuff (no pun intended!) ...
Okay, taking your example of a drug concentration of 100mg/l with a 2 hour half-life, the drug would be reduced as follows(?):
1PM 100 mg/l
3PM 50 mg/l
5PM 25 mg/l
7PM 12.5 mg/l
9PM 6.25 mg/l
11PM 3.125 mg/l
1 AM 1.56 mg/l (I suppose at this point the drug could be considered out of the body)Adding this up, I'm getting 6 half-lives, but you said that after FIVE half-lives, a drug is considered gone??
ALSO, what confuses me even more is what if the concentration was doubled, and it was 200 mg/l of the drug with a 2 hour half life -- wouldn't it take MORE half-lives to get rid of the higher concentration of the drug?
I would think that the higher the concentration of a drug, the more half-lives it would take to eliminate it???????
So, I don't understand how no matter what the concentration of a drug, it is always 5 half lives to eliminate it from the body??????? How can this be? HELP!!!!!!!!
Thanks!
Posted by Janelle on April 5, 2002, at 2:04:32
I'm sorry to post this again, but I'm afraid it will get *lost* above because I mistakenly typed it in all caps and then a post appeared just below it in caps, making the two posts hard to distinguish.
Here's my question:
Is there a relationship between how long it takes a drug to start working (e.g. 2 hours after being taken) and that drug's half life?
Meaning do drugs that take less time to start working also have shorter half-lives? Conversely, do drugs that take longer to start working also have longer half lives?
thanks!
Posted by Janelle on April 5, 2002, at 2:05:50
In reply to FACHAD: 2 questions 4 U (1/2 lives revisited!), posted by Janelle on April 4, 2002, at 23:50:20
Posted by Elizabeth on April 5, 2002, at 8:42:37
In reply to Relationship btw 1/2 life and onset of action?, posted by Janelle on April 5, 2002, at 2:04:32
AFAIk, you can't predict the time to onset of a drug's action based on its elimination half-life. The time it takes for a drug to start working has to do with things like how fast it's absorbed and taken up into the CNS, not with the rate of elimination.
HTH
-elizabeth
Posted by Elizabeth on April 5, 2002, at 8:52:24
In reply to Re: FACHAD:Thanks, great stuff, one teeny question: » Janelle, posted by fachad on April 4, 2002, at 22:04:53
> I think after 5 half lives have elapsed without any more doses the drug is considered effectively gone.
After 5 half-lives, there's 2^-5 = 1/32 = about 3% of the original amount left. My understanding is that after 7 half-lives the drug is considered to be effectively "gone" (at that point, less than 1% remains).
Of course, this depends on the amount taken in the first place. The elimination half-life also can differ depending on whether you've been taking the drug regularly, or just a single dose.
-elizabeth
Posted by fachad on April 5, 2002, at 11:51:28
In reply to FACHAD: 2 questions 4 U (1/2 lives revisited!), posted by Janelle on April 4, 2002, at 23:50:20
I think your question turns on exactly what you mean by the word "gone".
5 half-lives was what one pdoc told me was “gone enough” to be considered adequate for wash out to start another drug.
Elizabeth's 7 half lives uses a definition of "gone" as less than 1% of the original concentration remaining.
So it depends on what you mean by gone. If you mean totally absent from the body, even that is going to depend on how sensitive the equipment is that is used to analyze your blood.
If you had an analytical GC/MS set up that could detect concentrations down to ppt (parts per trillion) you might find a molecule or two of the drug floating around years after you stopped taking the drug.
But in science and medicine words like "gone" have *practical*, not *absolute* definitions. So if there is so little of the drug that it does not exert any clinical effects, or so little that it does not react with another drug, it is said to be gone, even if there's some really there.
Posted by IsoM on April 5, 2002, at 12:15:56
In reply to Relationship btw 1/2 life and onset of action?, posted by Janelle on April 5, 2002, at 2:04:32
Janelle, there's no relationship between the two & much depends on what drugs are being taken (& I don't just mean psych meds only). Some drugs just take a while before they exert their effect on the body as expected even when they reach their desired blood concentration. Other meds need to reach a steady-state plasma level before they work - it gets far more complicated - suffice to say half-life has no bearing on it.
Posted by Janelle on April 5, 2002, at 14:41:23
In reply to elimination half-life stuff, posted by Elizabeth on April 5, 2002, at 8:52:24
Posted by Janelle on April 5, 2002, at 14:45:06
How can the number of half lives required to eliminate a drug (5-7 half lives and it's gone from body) be the SAME for DIFFERENT concentrations of the drug?
Meaning, wouldn't a drug with a 100 mg/l concentration have fewer half-lives than one with say 350 mg/l concentration?
I don't get this! Please help! Thanks!
Posted by Janelle on April 5, 2002, at 14:46:52
In reply to How Many Half-Lives Until it's Gone? » Janelle, posted by fachad on April 5, 2002, at 11:51:28
Posted by Janelle on April 5, 2002, at 14:49:07
In reply to Re: Relationship btw 1/2 life and onset of action?, posted by Elizabeth on April 5, 2002, at 8:42:37
Posted by Janelle on April 5, 2002, at 14:56:44
In reply to How Many Half-Lives Until it's Gone? » Janelle, posted by fachad on April 5, 2002, at 11:51:28
Fachad - I had asked two questions about half-lives and elimination of meds, but you seem to have missed the second one so I've copy/pasted it here for you to please answer! Thanks:
------------------------------
2) Please humor me and bear with me a bit more here cuz I'm still not getting the whole story with this half-life stuff (no pun intended!) ...Okay, taking your example of a drug concentration of 100mg/l with a 2 hour half-life, the drug would be reduced as follows(?):
1PM 100 mg/l
3PM 50 mg/l
5PM 25 mg/l
7PM 12.5 mg/l
9PM 6.25 mg/l
11PM 3.125 mg/l
1 AM 1.56 mg/l (I suppose at this point the drug could be considered out of the body)Adding this up, I'm getting 6 half-lives, but you said that after FIVE half-lives, a drug is considered gone??
ALSO, what confuses me even more is what if the concentration was doubled, and it was 200 mg/l of the drug with a 2 hour half life -- wouldn't it take MORE half-lives to get rid of the higher concentration of the drug?
I would think that the higher the concentration of a drug, the more half-lives it would take to eliminate it???????
So, I don't understand how no matter what the concentration of a drug, it is always 5 half lives to eliminate it from the body??????? How can this be? HELP!!!!!!!!
Thanks!
Posted by Janelle on April 5, 2002, at 15:05:40
Example 2^-5 = 1/32
What function(s) are being done with the ^- part? Thanks.
Posted by JohnX2 on April 5, 2002, at 15:16:18
In reply to What does ^- mean in a computation?, posted by Janelle on April 5, 2002, at 15:05:40
> Example 2^-5 = 1/32
>
> What function(s) are being done with the ^- part? Thanks.This is exponentiation.
2^2 = 4
2^3 = 8
2^-5 = 1/(2^5) = 1/32redirect in the works...?
John
Posted by IsoM on April 5, 2002, at 15:19:30
In reply to ELIZabeth: what does ^- mean? (nm) » Elizabeth, posted by Janelle on April 5, 2002, at 14:41:23
The layout of the page Dr. Bob uses doesn't allow subscripts of superscripts to be used. So if someone wanted to write four squared equals sixteen, it would look like 4^2 = 16.
So 2^-5 = 1/32 means 2 raised to negative 5 equals 1/32. Might be a little clearer as 2^(-5). It's a simple math formula to figure out what's left after so many half-lives - in this case 5 half-lives (that's why a negative number is used).
Posted by IsoM on April 5, 2002, at 15:22:47
In reply to ELIZABETH: what do AFAIk and HTH stand for?! (nm) » Elizabeth, posted by Janelle on April 5, 2002, at 14:49:07
Posted by fachad on April 5, 2002, at 15:23:54
In reply to FACHAD: what does GC/MS stand for? (nm) » fachad, posted by Janelle on April 5, 2002, at 14:46:52
GC/MS = Gas Chromatography / Mass Spectrometry
It's a very sensitive analytical technique that chemists use to determine what chemicals are present in a sample, and at what concentrations they are present.
Here's a few links if you want to see more, but its heavy chemistry type stuff, so be forewarned:
http://www.shsu.edu/~chemistry/primers/gcms.html
http://ull.chemistry.uakron.edu/gcms/
http://www.home-healthtesting.com/gcmstests.htm
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