Even at the shortest end of the scale, diazepam has an 18 hour half-life. The average half-life [...] over 2 days. So the implications of that are variations of your intra-day dosing schedule are unlikely to have any real effect. Diazepam [...] commonly Rx'd 2X/day dosing, and that [...] NOT because of concerns about level blood concentrations. The reason for the usual 2X dosing [...] to spread the powerful sedating/depressant effect of the med.
So it's extremely unlikely that switching from 3X/day to 2X day will have any effect whatsoever (other than being more convenient!)
During my DLMT, I started at the usual 2X day, but varied the distribution widely, solely based on convenience. And at 3mg, I went to 1X/day, and all liquid. I never felt any effects from varying my doses throughout my taper.
Please refer to an old post of mine. It provides the math required to estimate the change in blood levels over time, based upon assumed half-life:
http://www.benzobuddies.org/forum/index.php?topic=6177.0By the way, for diazepam (if we include the active metabolites - which we should for our purposes), the lower half-life value [...] usually stated as 36 hours.
Let's assume that an individual metabolizes diazepam (Valium) at the extreme fast end. And let's also assume that a dose [...] taken twice per day, and blood levels have reached steady state (after extended regular use - some weeks or more).
So:
Half-life: 36 hours
Time between doses: 12 hours
12/36=0.333
0.5
0.333=0.7937
That's a drop in blood levels of just over 20%.
Now, let's try that with a 8h interval:
Half-life: 36 hours
Time between doses: 8h
8/36=0.222
0.5
0.222=0.856
That's a drop of 14.4%
Let's assume a more realistic 48 hours half-life (it varies from individual to individual).
And the patient doses three times per day, 8 hours apart:
Half-life: 48 hours
Dosing interval: 8 hours
8/48=0.16666
0.5
0.16666=0.89
That's an 11% drop to blood levels. The above calculations take no account of the absorption profile, but that [...] a relatively minor effect.
Now, let's repeat the above, with the dose taken just twice per day:
Half-life: 48 hours
Dose interval: 12 hours
12/48=0.25
0.5
0.25=0.84
I think a 16% drop [...] a significant enough difference from 11% (and the difference would be slighter greater for those who metabolize benzodiazepine faster than the assumed 48hour half-life).
But it [...] more complicated than this. Since the total daily dose [...] now split into two rather than three doses, the C
max value (maximum blood concentration) will rise. Though each dose [...] now 50% greater, maximum blood levels will not be 50% higher. This [...] because there [...] a greater fall in blood concentrations between doses, so it starts from a lower point. In short, blood levels oscillate a little more with the twice per day regimen, but the AUC (Area Under the Curve) - that's the total amount of the drug absorbed - should remain unchanged.
I do not have time to attempt to work out (or approximate) the actual blood concentrations for a given, chronically administered dose. But I expect the above to be about right and good enough for our purposes. Besides, I expect there are utilities on the Net to allow members to better model what occurs, depending upon the assumed staring values.
I am not suggesting that for a long half-life benzidiazepine like diazepam switching a daily dosing regimen from three to two (or vise versa) will be a great shock (so long as the total dose for the day remains unchanged), but there will be an effect. For some, I expect the effect will be noticeable.
