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!
poster:Sunnely
thread:101843
URL: http://www.dr-bob.org/babble/20020402/msgs/101880.html