More generally, the study of half-life reflects a measure of pharmacokinetics. Pharmacokinetics refers to the study of how a drug moves through the body—its entry, distribution, and elimination. Both pharmacists and physicians are concerned with a half-life as a metric. Nonetheless, as informed consumers, it’s a good idea for everyone to know a little bit about half-lives.
Formula
Here’s the formula for half-life: t1⁄2=[(0.693)(Volume of Distribution)]/Clearance
As demonstrated by the formula, a drug’s half-life is directly dependent on its volume of distribution or how widely the drug spreads throughout the body. In other words, the more widely the drug distributes in your body, the longer it half-life. Furthermore, this same drug’s half-life is inversely dependent on its clearance from your body. This means that when the rate of the drug’s clearance from your body is higher, then the half-life is shorter. Of note, drugs are cleared by both your kidneys and liver.
Examples
Here are some common drugs and their half-lives:
Oxycodone (pain medication): 2 to 3 hours Zoloft (antidepressant): 26 hours Phenobarbital (antiseizure medication): 53 to 118 hours Celebrex (NSAID or pain medication): 11. 2 hours
Kinetics
As a meaningful measure of pharmacokinetics, half-life applies to drugs with first-order kinetics. First-order kinetics means that the elimination of the drug directly depends on the initial dose of the drug. With a higher initial dose, more drug is cleared. Most drugs follow first-order kinetics.
Conversely, drugs with zero-order kinetics are independently cleared in a linear fashion. Alcohol is an example of a drug which is eliminated by zero-order kinetics. Of note, when the clearance mechanisms of a drug are saturated, as happens with overdose, drugs which follow first-order kinetics switch to zero-order kinetics.
Age
In older people, the half-life of a lipid-soluble (fat-soluble) drug increases on account of an increased volume of distribution. Older people usually have relatively more adipose tissue than do younger people. Age, however, has a more limited effect on hepatic and renal clearance. Because of the longer half-lives of drugs, older people often need lower or less frequent dosages of drugs than younger people do. On a related note, people who are obese have a higher volume of distribution, too.
With continuous administration (for example BID or twice-a-day dosing), after about four to five half-lives have elapsed, a drug reaches a steady-state concentration where the amount of drug eliminated is balanced by the amount being administered. The reason why drugs take some time to “work” is because they need to reach this steady-state concentration. On a related note, it also takes between four and five half-lives for a drug to clear from your system.
In addition to careful consideration of dosage in older people who experience longer drug half-lives, people with clearance and excretion issues should also be judiciously dosed by their prescribing physicians, too. For example, a person with end-stage renal disease (damaged kidneys) can experience toxicity from digoxin, a heart medication, after a week of treatment amounting to 0.25 mg a day or more.
