I am taking a pharmacology course, and I have a question concerning drug half-life. I understand the definition and concept of a half life. What I'm struggling to comprehend is why half-life of a drug does not depend on the dosage (concentration of the drug in the body). When talking about radioactive half-life, mass doesn't matter because all of the molecules are undergoing the same radioactive decay, which is dictated by laws of physics. However, in the body, the concentration of a drug in the body is dependent on the body's mechanisms of metabolism and elimination. Based on this I would assume that at some dose of a drug, it would be impossible for the body to reduce the amount of drug in the body to 50% in the amount of time specified by that drug's half life. For example, my text states that the half-life of morphine is 3 hours, and that this is the same whether 25 mg or 2 mg is given. Is there a dose of morphine that is so high that the body cannot reduce 50% in 3 hours? Why, also, does the body not reduce the level to 50% more quickly when less of a dose is given?
Thank you for your time, and I look forward to reading your answer.
For the first time in my 40 year long career as a pharmacologist, someone has asked a really challenging question.
You are right, there will be a dose of morphine (or any other drug) at which the body cannot metabolize (or excrete) 50 % of the drug in 3 hours (or the half life). The concept of half life does dictate such an occurrence. However, this dose of morphine would probably be too toxic. You will see such a phenomenon with alcohol. The half life of alcohol does change with dose, at high doses the half life is much longer than at lower doses, but for most drugs the half life is constant irrespective of the doses (within the clinical dose range)
Now let us examine the condition for most drugs. They are metabolized by enzymes which may be present in the liver or elsewhere. At high doses there is a higher chance of drug molecule coming in contact with an enzyme molecule than at lower doses. Hence metabolism will be slower at lower doses than at higher doses. If the number of enzyme molecules is limited then the rate of breakdown will depend upon the number of enzyme molecules rather than the drug molecules. If we bring in Avagadro's number , it will be clear that 1 Gram mole of drug and 1 gram mole of enzyme will contain an equal number of molecules. Since the mol wt of the drug is low (usually less than 500) while the mol wt of enzyme is high (usually around 500,000), drug molecules will exceed in number. Hence the rate of reaction will depend on enzyme molecule population rather than drug molecule population.
I dont know if I have been able to clarify your doubt, and I would like to send you a graph in this connection, but I am not sure if I can attach anything to this answer. If you send me your email I will be happy to send you some information in support of what I have written.
If you have any more doubts I will happy to try to clear it.