Drug Half-Life Explained

Anyone who has ever popped a cholesterol-lowering drug, or an antidepressant, or an anti-seizure medication, and expected to wake up the next day with a changed life knows that taking medicine is often a waiting game.

And anyone who has experienced an adverse side effect from a drug, and is waiting anxiously for it to clear the system, knows the same.

Both the time it will take for a drug to be effective, and the time it will take for it to leave the body completely, depend on a drug's half-life.

The half-life is the amount of time necessary for the concentration of the drug in the bloodstream of the body to be reduced by one-half. The time it will take for a drug to reach a steady state, or full effectiveness, in the system is based on that half-life.

And sometimes it just isn't all that fast.

A presentation from the University of Florida entitled "Basic Biopharmaceutics" clarifies that, "It takes [a medication] one half-life to reach 50%, 2 half-lives to reach 75%, 3 half-lives to reach 87.5%, 3.3 half-lives to reach 90%, 4 half-lives to reach 93.75% of steady state. In most clinical situations, the attainment of steady state can be assumed after 3-5 half-lives."

As you can see, two halves do not make a whole. That lengthy stretch is the same amount of time it will take for the drug to be eliminated from the system.

The presenters use the example of Klonopin (clonazepam), a medication for anxiety.

Using the longest estimate of Klonopin's half-life, 50 hours, it would be 50 hours times 5 (using the larger of the above half-life estimates), to equal 250 hours or 10.42 days. That means it takes around 10 days for Klonopin to reach a study state in the blood stream and achieve a full effect--and the same amount of time for the system to be clear of it.

The length of a drug's half-life is significant when the medication is used to treat chronic symptoms, or when a patient's body needs to be clear of the drug in order to take the next step in treatment.

For example, some medications are known for having short half-lives, which means the body eliminates them quickly. That sounds good, but, since minimum blood levels of a drug have to be maintained for a medicine to be effective, drugs with shorter half-lives have to be given in more frequent doses.

Unfortunately for those suffering from anxiety, tranquilizers like benzodiazepines (the aforementioned Klonopin, Xanax [alprazolam] and Ativan [lorazepam]) are eliminated from the body and reduced in strength quickly. This is less than ideal for the person who takes them to fight feelings of agitation and create a sense of calm. The calm wears off rather quickly, leading to increases in anti-anxiety doses. Since addiction results from the need to take more medication to keep the effect going, the short half-life can lead to undesirable problems.

Over the counter pain relievers have the same half-life problem. Pain tends to return relatively quickly after taking Tylenol or Advil.

In contrast, when a drug's half-life is long, it stays in the body without losing potency for quite some time. This can pose a problem as well.

For example, the antidepressant Prozac (fluoxetine) has a long half-life. If a patient's depression fails to remit on Prozac, before the doctor can switch to another class of antidepressants which may cause unfavorable interactions, the patient may need to wait weeks uncovered by any antidepressant before beginning her new pill. The older line treatment of MAOI's (e.g. Parnate) are incompatible with the SSRI's  (e.g. Prozac).

Blood thinner Coumadin (warfarin) also has a long half-life. Because Coumadin's very purpose is to prevent the blood from clotting, should a person on Coumadin need emergency surgery, he's at risk of heavy and dangerous bleeding.

Sometimes a longer half-life can increase a drug's popularity.

Although Viagra, as the first drug to treat erectile dysfunction, will always hold a sacred place in the western male psyche, competitor Cialis (tadalafil) has a longer half-life, allowing it to accumulate in the body if taken regularly-- a real selling point to many men. While Viagra's half-life is 4 hours, Cialis' is 17, which means, as GlobalChange.com calculates, 25% of a Cialis dose is still in the body after 35 hours and 12.5% after over 50 hours. This clearly leads, if the drug is taken regularly, to accumulation of it in the body, making sex at any time a practical possibility.

The amount of variability in drug half-lives is large.

For example, the half-lives of the following drugs are less than two hours: Aspirin, Heparin (same generic name) to treat blood clots, Aldoment (methyldopa) to treat high blood pressure, and Narcan (naloxone), to counteract the effects of opiate overdose.

Painkiller Morphine's half-life is 2-3 hours, which explains why post-surgical patients are so uncomfortable with the 4-hour dose regimen used in most hospitals.

Antidepressants Elavil (amitriptyline) and Tofranil (imipramine) and anti-asthma medication Aerolate (theophylline) all have half-lives between 10 and 24 hours.

Prozac's (fluoextine) is 4-6 days, Avodart's (dutasteride), to treat enlargement of the prostate gland, is a full 5 weeks, and Cordarone's (amiodarone), to treat abnormal heart rhythm, is over 100 days.

Certain illnesses can decrease the rate of drug elimination, and therefore increase a drug's half-life:

1. Kidney disease that causes decreased excretion
2. Decreased metabolism, as, for example, occurs with cirrhosis of the liver
3. Decreased renal blood flow, or a lesser volume of blood delivered to the kidneys in a given amount of time, as would occur in heart failure, a heart attack, or extensive bleeding.

Calculating a Drug’s Half-Life - Formula

Calculating a drug's half-life can be a bit complex, if you don't have websites like ours to help you. The formula is as follows:

with CL referring to clearance, or measure of the body's ability to eliminate a drug,  and V_D indicative of volume of distribution, which relates the amount of drug in the body to the concentration of the drug in the blood.

Failing the ability to compute this formula, your best bet is to drink lots of water when you're hoping to eliminate a drug from your system.  And be careful of self-dosing with left-over prescriptions or OTC meds.  You don't know what's lurking in your bloodstream.