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Dear members,
In a study we calculated the PK parameters of a drug after IV and I'M
injections as follow.
After IV administration (5 mg/kg body weight) t1/2beta (1.69 hours),
Vd(ss) (2.61 l/kg)
After I'M administration (5 mg/kg body weight) t1/2beta (2.63hours),
Vd(area) (1.87 l/kg), F(83%) .
My question is what dose should we give to maintain a Css(AV) of
0.12mcg/ml with a dosing interval of 12 hours by intramuscular route?
Kindly give equations (formulas) that are used to calculate such
dosages.
comments awaited.
Thanks
Bhavsar S.K.
INDIA
skbhavsar.at.gau.guj.nic.in
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Bhavsar,
One easy way of dose calculation to achieve a steady state
concentration of .12mg/l is to use the following equation:
Cssave= FSD/Tau*Cl
FSD= Cssave*Tau*Cl
D= Cssave*Tau*Cl/FS
D= (.12mg/l)(12hrs)(1.87 l/kg)(.263498 hr1)/(0.83)(1)
Dose= .85487 mg/kg
F= fraction absorbed= 0.83
S= salt form= 1
Cssave= steady average plasma concentration= 0.12mg/l
Tau= dosage interval in hrs= 12hrs
Beta= .693/T1/2 beta= .263498 hr1
Cl= clearance= beta*Vd= (.263498 hr1)(1.87 l/kg)= .49724 l/kg*hr
Mike Leibold, PharmD, RPh
ML11439.at.goodnet.com
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Css (ave) = AUC/T or FD/Vd.k T (T = dosing interval). Hope this helps.
Srikumaran Melethil, Ph.D.
Professor of Pharmaceutics and Medicine
University of MissouriKC
203 B Katz Hall, School of Pharmacy
5005 Rockhill Road
Kansas City, MO 64110
8162351794 (voice); 8162355190 (fax)
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Mike,
I think your answer shows knowledge of PK but not of the usual rules
of precedence for mathematical operators:
> Cssave= FSD/Tau*Cl
I think you meant:
> Cssave= FSD/Tau/Cl
although it would be more generally true (and simpler?) to write:
> Cssave= Rate/Cl
Why make something simple more complicated by introducing "beta" and
"vd" which imply a one compartment model and also imply, incorrectly,
that CL depends on Vd?
> Beta= .693/T1/2 beta= .263498 hr1
> Cl= clearance= beta*Vd= (.263498 hr1)(1.87 l/kg)=
>.49724 l/kg*hr

Sender: PharmPK.at.boomer.org
ReplyTo: Nick Holford
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From: Nick Holford
Date: Tue, 28 Nov 2000 09:57:59 +1300
To: david.at.boomer.org
Subject: Re: PharmPK Re: Dose calculation for IM injections
The following message was posted to: PharmPK
Srikumaran Melethil,
I think your answer shows knowledge of PK but not of the usual rules of
precedence for mathematical operators:
> Css (ave) = AUC/T or FD/Vd.k T (T = dosing interval)
I think you meant:
> Css (ave) = AUC/T or FD/Vd/k T (T = dosing interval)
although it would be more generally true (and simpler?) to write:
> Css (ave) = Rate/CL
Why make something simple more complicated by introducing "k" and "Vd"
which imply a one compartment model and also imply, incorrectly, that CL
depends on Vd?

Sender: PharmPK.at.boomer.org
ReplyTo: Nick Holford
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From: Nick Holford
Date: Tue, 28 Nov 2000 10:09:56 +1300
To: david.at.boomer.org
Subject: [Fwd: PharmPK Re: Dose calculation for IM injections OOPS!]
The following message was posted to: PharmPK
OOPS!
>
> I think you meant:
> > Css (ave) = AUC/T or FD/Vd/k T (T = dosing interval)
I should also have inserted a "/":
> > Css (ave) = AUC/T or FD/Vd/k/T (T = dosing interval)

Nick Holford, Divn 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)3737599x6730 fax:3737556
http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm
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Dear Dr. Holford,
I believe what I have written is as simple as what you have written.
It is just
a matter of your opinion.
In many cases, a twocompartment (given IV) drug can be treated as a
onecompartment. So, there is no problem with what I have written.
Are you suggesting we get rid of volume terms in PK?
Srikumaran Melethil, Ph.D.
Professor of Pharmaceutics and Medicine
University of MissouriKC
203 B Katz Hall, School of Pharmacy
5005 Rockhill Road
Kansas City, MO 64110
8162351794 (voice); 8162355190 (fax)
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Melethil, Srikumaran K. (by way of David_Bourne)" wrote:
> I believe what I have written is as simple as what you have written.
> It is just a matter of your opinion.
You wrote this (I have corrected the mathematical operator errors):
Css (ave) = AUC/T or FD/Vd/k/T (T = dosing interval)
I wrote this:
Css (ave) = Rate/CL
I cannot see how your expression involving F,D,Vd,k and T ( 5 terms)
is as simple as mine even if I rewrite it as follows ( 4 terms).
Css (ave) = FD/T/CL
It is my opinion that 4 terms are simpler than 5 terms.
> In many cases, a twocompartment (given IV) drug can be treated as a
> onecompartment. So, there is no problem with what I have written.
I have no disagreement that under suitable circumstances a one
compartment model is a reasonable approximation to a two compartment
model and that both may be reasonable approximations to reality. But
I cannot see what this has to do with the prediction of average
steady state concentrations. The expressions we have both suggested
are totally independent of any assumption about the number of
compartments except this number is greater than zero.
> Are you suggesting we get rid of volume terms in PK?
My comment was intended to point out that CL is a fundamental** PK
parameter describing the relationship between mass transfer rates and
concentration:
Rate = CL * C
Look! No Vd! No k! Just CL!
I am indeed suggesting that we get rid of volume terms from PK when
we are applying PK to predict average steady state concentrations.
** Roger Jelliffe pretends he has never heard of this although he and
I (and many others no doubt) have discussed it on many occasions.

Nick Holford, Divn 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)3737599x6730 fax:3737556
http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm
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