PharmPK Discussion List Archive Index page
• On 23 Feb 2003 at 07:05:51, jagadeesh gouda (jaggagouda.at.yahoo.co.in) sent the message
`The following message was posted to: PharmPKdear pharma pk friends  Can u give me equation for loading dose andmaintainance dose calculation  for sustained releasesolid dosageform from pharmacokinetics of drug .jagadeesh tFormulation developmentAristo pharmaMADHYAPRADESHINDIA[Lots of equation on my website at http://www.boomer.org/c/p1/ andhttp://www.boomer.org/c/p3/ (and others) but what release/absorptioncharacteristic do you expect for the components of your sustainedrelease formulation..i.e fast first order with slow zero order or slowand fast first order, e.g. - db]`
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• On 27 Feb 2003 at 10:36:55, "Melethil, Srikumaran K." (melethils.at.umkc.edu) sent the message
`The following message was posted to: PharmPKDear Jagadeesh,Assuming a one-compartment model and zero-order release:LD = Vd *Cpss/F;   where LD is the loading dose, Vd is the volume ofdistribution and Cpss is the steady state concentration you wish tomaintain and F is the bioavailable fraction.MD  = (Cpss*Vd*k*T)/F where MD is the maintenance dose; k is theoverall elimination rate constant and  T is the release time.Hope this helps.Srikumaran K. Melethil, Ph.D., J.D.Professor Emeritus, PharmaceuticsUniversity of Missouri- Kansas City`
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• On 28 Feb 2003 at 08:23:30, Nick Holford (n.holford.-a-.auckland.ac.nz) sent the message
`The following message was posted to: PharmPK> Assuming a one-compartment model and zero-order release:>> LD = Vd *Cpss/F;   where LD is the loading dose, Vd is the volume of> distribution and Cpss is the steady state concentration you wish to> maintain and F is the bioavailable fraction.>> MD  = (Cpss*Vd*k*T)/F where MD is the maintenance dose; k is the> overall elimination rate constant and  T is the release time.>Algebraically OK but physiologically wrong. The average steady stateconcentration and thus the maintenance dose rate is NOT affected byvolume of distribution. It is determined by clearance (CL):MD  = (Cpss*CL*T)/FThe point of this distinction is to emphasize that if you have factorsthat affect volume of distribution e.g. altered body composition inobesity, which do not affect elimination then the loading dose mayrequire adjustment but the maintenance dose rate does not need tochange.Nick Holford, Divn Pharmacology & Clinical PharmacologyUniversity of Auckland, 85 Park Rd, Private Bag 92019, Auckland, NewZealandemail:n.holford.-a-.auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556http://www.health.auckland.ac.nz/pharmacology/staff/nholford/`
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• On 27 Feb 2003 at 12:24:51, ehab eldesoky (ehegypt.-at-.yahoo.com) sent the message
`The following message was posted to: PharmPKDr.Srikumaran K. Melethil,In your reply, I would like please to clarify twopoint:T= release time. do you mean dose interval?cpss= what concentration we select for the equation.Is it average or trough steady state concentration?.Thank YouEhab EL Desoky M.D.Assiut University. Egypt`
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• On 27 Feb 2003 at 16:30:28, "Melethil, Srikumaran K." (melethils.-a-.umkc.edu) sent the message
`The following message was posted to: PharmPKDear Dr. Desoky,No, T is not the dosing interval;  T is  time over which you want thedrug to be released at the site (e.g., 12 hr, 8 hr etc). If the dosinginterval and T are equal, then it  mimics continuous infusion. In thatcase, there is no peak or trough; it can be used as an average, when Tand the dosing interval are not the same.Srikumaran K. Melethil, Ph.D., JDProfessor Emeritus, PharmaceuticsSchool of PharmacyUniversity of Missouri- Kansas City`
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• On 28 Feb 2003 at 12:45:32, Nick Holford (n.holford.at.auckland.ac.nz) sent the message
`The following message was posted to: PharmPK"Melethil, Srikumaran K." wrote:>> No, T is not the dosing interval;  T is  time over which you want the> drug to be released at the site (e.g., 12 hr, 8 hr etc). If the dosing> interval and T are equal, then it  mimics continuous infusion. In that> case, there is no peak or trough; it can be used as an average, when T> and the dosing interval are not the same.The original model proposed by Prof Melethil was> MD  = (Cpss*Vd*k*T)/F where MD is the maintenance dose; k is the> overall elimination rate constant and  T is the release time.The usual interpretation of Cpss in this context is that it means theaverage steady state concentration. In that case the maintenance dose Tmust be interpreted as the dosing interval. The time course of releaseof the formulation makes no difference because the averageconcentration reflects the integral of conc over time and thus time isnot relevant.Rate In = Rate Out              ; mass balance basis for this modelMDR     = CL/F * CPssavg        ; maintenance dose rate for target ofCPssavgMD      = MDR * Dosing Interval ; intermittent maintenance dose withregular dosingIMHO there is no simple interpretation of what Cpss means if T is therelease time of the formulation and T is not equal to the dosinginterval. Perhaps Prof Melethil would enlighten us?NickNick Holford, Dept Pharmacology & Clinical PharmacologyUniversity of Auckland, 85 Park Rd, Private Bag 92019, Auckland, NewZealandemail:n.holford.-at-.auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556http://www.health.auckland.ac.nz/pharmacology/staff/nholford/`
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