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Dear list,
I have a perhaps very simple question. Some wher I found a calculation for
accumulation of drugs with
R=1/(1-eEXP-Ke t)
where R is the accumulation factor, t is the dosing frequency in hours and
Ke=ln2/t1/2.
What does R is saying to me, perhaps with results R<1 or R>1?
Thanks for any answers
T. Hoppe-Tichy
Heidelberg, Germany
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Dear T. Hoppe-Tichy
This equation is an alternative to more formal calculations of the
accumulation factor R.
R can be calculated as the ratio of drug concentrations observed during a
dosing interval at steady-state divided by drug concentrations seen during
the dosing interval after a single (first) dose, as described by the
following equations:
R= steady state AUC(0-tau) / single dose AUC(0-tau) where tau is dosing
interval.
Also, calculated by: R=Cmin(steady-state) / Cmin(single-dose)
Note: steady state AUC(0-tau) is equal to AUC(0-infinity) after a single
dose.
If your dosing interval is long enough such that all drug is eliminated
before a subsequent dose, the resulting R value = 1, since both the numerator
and denominator should be equal, and obviously no accumulation will occur.
The equation R=1/(1-e^-Kel t) presented in your e-mail, represents a
simplified way of calculating R without the need to obtain steady-state
data. As can be seen in this equation, R is a function of tau and the
terminal elimination rate constant (and is independent of dose). Longer kel
and shorter tau will result in R>1. Technically, R should never go below 1
(unless someone knows of situations of metabolic induction, etc. that may
produce artifactual results?).
Best Regards
Dave Jaworowicz
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Dear all,
I would appreciate if any members of PharmPK can advise me on how to
calculate (and interpret) theoretical accumulation ratio (AR) when
using a two-compartment model.
Thank you;
Nicolas GREGOIRE.
[Moderator note - I have received a few messages recently that start
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Nicolas,
You might want to see if you can get a copy of the article by Meinke
I & Gleiter GH: Asessment of drug accumulation in the evaluation of
phharmacokinetic data. J Clinical Pharmacol 1998; 38:680-684.
Bert Lum
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Nicolas
An old but good reference to the calculation of Accumulation ratio:
Wayne Colburn; Estimating the accumulation of drugs, 1983, J Pharm
Sci;72:633-634
regards
Brian
Brian E. Davies
Clinical Director, PDMP
Hoffmann-La Roche, Nutley, NJ
* brian.davies.-a-.roche.com
*(973) 235-2053
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References on accumulation ratio:
Wagner JG - J Clin Pharmacol &:84-88, 1967
Chiou WL - J Pharmacokin Biopharm 8:311-318, 1980
Van Rossum - Arch Int Pharmacodyn 188: 200-203, 1970
hope these help
gary
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