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The following message was posted to: PharmPK
Dear sir,
The oral dosing range of a drug which undergoes extensive first
pass metabolism is 5-50mg/kg/day for 7 weeks in rats.The drug is
having following pharmacokinetic characteristics when given by
oral route.
Absorption- 60-80%
Tmax (hr)- 1.2- 2.3
Cmax (ng/ml)- 10-35
Bioavailability - 5%
t1/2(hr) - 2-3
What should be the dose and dosing schedule of the same drug for
IV administration in rats?
Thank you,
Regards
Satyawan
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The following message was posted to: PharmPK
My approach would be the following.
As you want to dose IV you will not be able to avoid the first pass
metabolism. To set up your IV dose you should consider the absorbed
percentage (60-80%) and not the bioavailable one (5%).
Let's say that the rat weight is 250g. The total blood volume is
roughly 10 to 15 mL. If you need to read the same range of blood
concentration (10-35 ng/mL) you should dose at least at:
35*15/0.6=875ng per rat if there is no distribution event interfering.
If I were you I would have a try at 1mg per rat and would prepare a 4
mg/mL IV solution to be dosed at 1mL/kg. And then I would adjust the
dose regarding the results of this study to be as close to your "oral"
blood concentrations as possible.
I hope this makes sense
Regards,
Frederic
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The following message was posted to: PharmPK
Dear Satyawan,
You asked:
> What should be the dose and dosing schedule of the same drug for
> IV administration in rats?
I guess my question would be: What do you want to achieve by oral
dosing? Are you aiming at achieving the same average steady state
concentration after the po dose by giving the drug intravenously? Or is
it Cmax you are trying to maintain?
You have also provided some useful, but incomplete information. What
are the CL/F and Vd/F values of the compound?
I also have a rather personal question. I am interested to know how the
%absorption of the compound after the oral dose (60-80%) was estimated.
Could you provide some details?
Toufigh Gordi
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The following message was posted to: PharmPK
Dear frederic,
thanks for your insight but I am not able to understand the
explanation to the question I asked
"As you want to dose IV you will not be able to avoid the first
pass metabolism."
well I think the FPM will be bypassed when given by IV route
"To set up your IV dose you should consider the absorbed
percentage (60-80%) and not the bioavailable one (5%)."
we take 100% bioavailability when IV route is taken into account
and not 60-80% as is in the case of oral route
and kindly do explain the calculation by which the IV dose of
1mg/rat is arrived.
thank you
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The following message was posted to: PharmPK
Dear Toufigh,
thanx for the reply.
As I am looking for the same therapeutic efficacy as that achieved
by PO,I would go for achieving the Css rather than Cmax by IV
route.
the Vd being 0.5, so Vd/F is) 0.5/5 =0.1
I don't have CL value.
I am still unclear about the dose and dosing schedule by IV
route.
As the p'kinetic parameters I had furnished (human subjects) are
reported in the literature, I don't have much idea about
calculation of %absorption value. But I guess one can sample the
portal vein and determine the conc. of premetabolized drug.
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