N&PD Moderators: Skorpio | someguyontheinternet
Slow_Mobius and all,
I would appreciate your comments, especially to post #50.
Decisions, decisions ...
Kittycat5,
Question: sources give a half life for diazepam of about 1-2 days. However, diazepam accumulates up to 5-8 times the daily dose. What does half life mean in that situation ? From what I get, it is slowly released from the fat cells and other parts of the body.
What I mean is, half of the diazepam won't be eliminated in two days. Is there a phrase for that particular type of 'half life' ?
Ok, lets start again. As I mentioned, pharmacokineticists will model the body into compartments with the single compartment model the most basic. In this model, the drug is absorbed, distributed, exerts its effects, is metabolized and is eliminated from one ideal physiological "box."
But in reality, this model is too simple to explain various PK and PD effects of benzos and many other drugs. A multi-compartment (usually 2 or 3) model is a far better tool when trying to understand PK of a drug.
Valium can be modeled as a 2 or 3 compartment system. I should probably say here, that this info generally pertains to IV administration but I believe oral Triazolam follows similar patterns. As I said before, the distribution phase is usually for IV ROA. A concentration v time graph of IV diazepam will show an initial rapid climb to Cmax, followed by a shorter but still quick distribution phase where levels drop sharply followed by a slower, steadier decrease in plasma levels in the elimination phase. This corresponds to the 2 or 3 compartments. The rapid climb in the first phase would be the central compartment and the distribution and elimination phases can be thought of either together as the second compartment or separate as compartment 2 and 3. As drugs distribute to various tissues, they leave the plasma at a rate very much like the terminal elimination half life, albeit much faster. This is often called the distribution t1/2. Again, I must state this all applies to IV admin and the decrease in drug levels is in the blood, not tissue.
After distribution into the various tissues or compartments occurs, the drug will start to redistribute back into the circulation and the slow steady decline of elimination occurs who's rate is called the elimination half life. It should be noted this rate is the same for IV and oral routes.
I know I didnt fully answer your question yet, Kdem but I am getting there. I am making a new post as I lost some of this one again. It is cursed.