# PharmPK Discussion - Accumulation ratio calculation

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• On 12 Apr 2002 at 10:18:21, "Hoppe-Tichy, Torsten" (Torsten_Hoppe-Tichy.aaa.med.uni-heidelberg.de) sent the message
`Dear list,I have a perhaps very simple question. Some wher I found a calculation foraccumulation of drugs withR=1/(1-eEXP-Ke t)where R is the accumulation factor, t is the dosing frequency in hours andKe=ln2/t1/2.What does R is saying to me, perhaps with results R<1 or R>1?Thanks for any answersT. Hoppe-TichyHeidelberg, Germany`
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• On 12 Apr 2002 at 14:17:33, David Jaworowicz (david.jaworowicz.-at-.cognigencorp.com) sent the message
`Dear T. Hoppe-TichyThis equation is an alternative to more formal calculations of theaccumulation factor R.R can be calculated as the ratio of drug concentrations observed during adosing interval at steady-state divided by drug concentrations seen duringthe dosing interval after a single (first) dose, as described by thefollowing equations:R= steady state AUC(0-tau) / single dose AUC(0-tau) where tau is dosinginterval.Also, calculated by: R=Cmin(steady-state) / Cmin(single-dose)Note: steady state AUC(0-tau) is equal to AUC(0-infinity) after a singledose.If your dosing interval is long enough such that all drug is eliminatedbefore a subsequent dose, the resulting R value = 1, since both the numeratorand denominator should be equal, and obviously no accumulation will occur.The equation R=1/(1-e^-Kel t) presented in your e-mail, represents asimplified way of calculating R without the need to obtain steady-statedata.  As can be seen in this equation, R is a function of tau and theterminal elimination rate constant (and is independent of dose).  Longer keland shorter tau will result in R>1.  Technically, R should never go below 1(unless someone knows of situations of metabolic induction, etc. that mayproduce artifactual results?).Best RegardsDave Jaworowicz`
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• On 28 May 2002 at 12:44:16, (icrgregoire.-a-.yahoo.com) sent the message
`Dear all,I would appreciate if any members of PharmPK can advise me on how tocalculate (and interpret) theoretical accumulation ratio (AR) whenusing a two-compartment model.Thank you;Nicolas GREGOIRE.[Moderator note - I have received a few messages recently that startwith 'PharmPK' in the subject line. The problem is that I have thelistserv software set up to add this to the subject on the way out.Thus, messages with PharmPK in the beginning of the message look tome like messages that have already been sent out and I may 'ignore'them. Thus, the best approach is to send the message toPharmPK.-a-.boomer.org with a descriptive subject without using PharmPK.Replying to a message with a comment on the same topic usually workswell as a Re: (or similar) is usually added and this cues me torecognize a new message  Thanks - db]`
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• On 29 May 2002 at 12:14:18, "Bert L. Lum" (bert.lum.aaa.coastside.net) sent the message
`Nicolas,You might want to see if you can get a copy of the article by MeinkeI & Gleiter GH: Asessment of drug accumulation in the evaluation ofphharmacokinetic data. J Clinical Pharmacol 1998; 38:680-684.Bert Lum`
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• On 29 May 2002 at 13:59:53, "Davies, Brian {CLIN~Nutley}" (BRIAN.DAVIES.at.ROCHE.COM) sent the message
`NicolasAn old but good reference to the calculation of Accumulation ratio:Wayne Colburn; Estimating the accumulation of drugs, 1983, J PharmSci;72:633-634regardsBrianBrian E. DaviesClinical Director, PDMPHoffmann-La Roche, Nutley, NJ* brian.davies.-a-.roche.com*(973) 235-2053`
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• On 30 May 2002 at 10:14:06, thompson.ga.-at-.pg.com sent the message
`References on accumulation ratio:Wagner JG - J Clin Pharmacol &:84-88, 1967Chiou WL   - J Pharmacokin Biopharm 8:311-318, 1980Van Rossum - Arch Int Pharmacodyn 188: 200-203, 1970hope these helpgary`
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