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Dear All,
I would like to know, in case of an infusion stopped at 24 hrs:
1. what would be the cmax
2.For calculating Vd, we would need the extrapolated value back to the
y axis intercept?
Cordially,
Gupta
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The following message was posted to: PharmPK
It is depend upon the t1/2 of your drug. if your drug has short half-
life then my be the plasma concentration is reaching steady state and
the level will be your the maximum plasma concentration produce by the
rate of infusion will be the Cpss and Vd will be simply calculated
from the following equation
R0 = CPss.Vd.Kel
If the t1/2 is long then the maximum plasma concentration produce by
the rate of infusion will be calculated from the intercept.
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Dear David,
The infusion is of Methotrexate, which has a t1/2 of 3-15 hours, and
has a three phase elimination. The infusion was stopped at 24 hours,
and samples were collected at 24, 36, 48, 72 hrs post infusion. When
the values are plotted on semi log curve, it is a straight line, which
shows a one compartment model. Can drug llike methotrexate, with
three phase elimination (though first phase of distribution is quite
short) give a one compartmental model of distribution? How is the drug
behavior in this case, as the results seem to a monoexponential decay
akin to IV bolus dose?!
Cordially,
Gupta
[Once the first and second faster phases have completed five half-
lives the last phase is all that is left and you will get a mono-
exponential decline. Play with the applet at
http://www.boomer.org/c/p4/ja/Fig1966/Fig1966.html
set the slow k0 to 0.1 (or less, it doesn't like 0) and try increasing
the Duration (you will also need to change the y-axis using the set
axis button) - db]
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The following message was posted to: PharmPK
Hi Gupta,
We did some work many years ago on Methotrexate following 24 hours
infusion.
Mould GP, Aherne GW, Morris BA, Teale JD and Marks V. Radioimmunoassay
of
drugs and its clinical application. European Journal of Drug
Metabolism and
Pharmacokinetics,(1977), 4, 171-184.
Aherne GW, Piall E, Marks V, Mould GP and White WF. Prolongation and
enhancement of serum methotrexate concentrations by probenecid. British
Medical Journal, (1978), 1, 1097-1099.
When we measured over the first 24 hours after stopping the infusion,
the
kinetic profile was biexponential and in the paper above we postulated
on
the '3rd phase'.
Graham
Graham Mould, PhD
Consultant Pharmacist
Email: gmould.-at-.gcpl.co.uk
Web: www.xpertwitness.co.uk
XPC Services
Surrey Technology Centre
Surrey Research Park, Occam Road
Guildford, Surrey GU2 7YG
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Hi,
I want to know how to calculate cmax, tmax and AUC in this case when
infusion of methotrexate has been stopped at 24 hrs...
Cordially,
Gupta
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