Back to the Top
The following message was posted to: PharmPK
dear pharma pk friends
Can u give me equation for loading dose and
maintainance dose calculation for sustained release
solid dosageform from pharmacokinetics of drug .
jagadeesh t
Formulation development
Aristo pharma
MADHYAPRADESH
INDIA
[Lots of equation on my website at http://www.boomer.org/c/p1/ and
http://www.boomer.org/c/p3/ (and others) but what release/absorption
characteristic do you expect for the components of your sustained
release formulation..i.e fast first order with slow zero order or slow
and fast first order, e.g. - db]
Back to the Top
The following message was posted to: PharmPK
Dear Jagadeesh,
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.
Hope this helps.
Srikumaran K. Melethil, Ph.D., J.D.
Professor Emeritus, Pharmaceutics
University of Missouri- Kansas City
Back to the Top
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 state
concentration and thus the maintenance dose rate is NOT affected by
volume of distribution. It is determined by clearance (CL):
MD = (Cpss*CL*T)/F
The point of this distinction is to emphasize that if you have factors
that affect volume of distribution e.g. altered body composition in
obesity, which do not affect elimination then the loading dose may
require adjustment but the maintenance dose rate does not need to
change.
Nick Holford, Divn Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
email:n.holford.-a-.auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
Back to the Top
The following message was posted to: PharmPK
Dr.Srikumaran K. Melethil,
In your reply, I would like please to clarify two
point:
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 You
Ehab EL Desoky M.D.
Assiut University. Egypt
Back to the Top
The following message was posted to: PharmPK
Dear Dr. Desoky,
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.
Srikumaran K. Melethil, Ph.D., JD
Professor Emeritus, Pharmaceutics
School of Pharmacy
University of Missouri- Kansas City
Back to the Top
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 the
average steady state concentration. In that case the maintenance dose T
must be interpreted as the dosing interval. The time course of release
of the formulation makes no difference because the average
concentration reflects the integral of conc over time and thus time is
not relevant.
Rate In = Rate Out ; mass balance basis for this model
MDR = CL/F * CPssavg ; maintenance dose rate for target of
CPssavg
MD = MDR * Dosing Interval ; intermittent maintenance dose with
regular dosing
IMHO there is no simple interpretation of what Cpss means if T is the
release time of the formulation and T is not equal to the dosing
interval. Perhaps Prof Melethil would enlighten us?
Nick
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
email:n.holford.-at-.auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)