- On 12 Apr 2002 at 10:18:21, "Hoppe-Tichy, Torsten" (Torsten_Hoppe-Tichy.aaa.med.uni-heidelberg.de) sent the message

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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 - On 12 Apr 2002 at 14:17:33, David Jaworowicz (david.jaworowicz.-at-.cognigencorp.com) sent the message

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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 - On 28 May 2002 at 12:44:16, (icrgregoire.-a-.yahoo.com) sent the message

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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.

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recognize a new message Thanks - db] - On 29 May 2002 at 12:14:18, "Bert L. Lum" (bert.lum.aaa.coastside.net) sent the message

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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 - On 29 May 2002 at 13:59:53, "Davies, Brian {CLIN~Nutley}" (BRIAN.DAVIES.at.ROCHE.COM) sent the message

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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 - On 30 May 2002 at 10:14:06, thompson.ga.-at-.pg.com sent the message

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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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