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For a drug with longish t1/2 (9 hr) and small Vd (0.1 L/kg) in
healthy subjects, similar Cmax values were observed at the end of a 2
min infusion as at the end of a 30 min infusion (crossover study,
bloods at end of infusion). Is this possibly due to incomplete
distribution at 2 minutes or some other cause? Drug renally cleared.
Thanks,
Dave
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The following message was posted to: PharmPK
HI Dave,
Simulation is the best tools to help you understand this result.
Estimate your parameters from your first experiment and simulate.
Hope this helps
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The following message was posted to: PharmPK
Hi Dave,
Cmax is always achieved at the end of the infusion and it is determined
by the dose you administer. Small Vd indicates that no extensive
distribution into tissues can be expected but disposition to
intravascular compartment only (6 L for a 60-kg man). After two minutes
it is distributed in the compartment and that's it. The long half-life
does not play a role in the distribution kinetics, although some drug is
eliminated during the early moments, the fraction of the drug lost
during the distribution phase is small, even after 30 min infusion.
Regards
Mat
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The following message was posted to: PharmPK
Dave,
With a half life of 9h, the clearance within 2 min or 30 min would
not be so
much different, so assuming the doses were the same for the two
infusions,
Cmax would not be so different either, because you have about the same
amount of drug in the same volume at the end of both infusions. There
should
be no need to invoke incomplete distribution to explain your data.
Walt Woltosz
Chairman & CEO
Simulations Plus, Inc. (AMEX: SLP)
42505 10th Street West
Lancaster, CA 93534-7059
U.S.A.
http://www.simulations-plus.com
E-mail: walt.-at-.simulations-plus.com
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