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The following message was posted to: PharmPK
Dear Colleagues,
I need to calculate the half-life of endogenous LH in
hypogonadotrophic subjects. They all have
hypogonadotrophic hypogonadisam (LHRH deficiency).
All subjects were primed for a week by the subcutaneous
LHRH pulsatile infusion, and then LHRH bolus was given i.v
and LH response was measured. What would be the best way
to calculate LH half-life, and what software to use?
(Using exogenous LH would be inappropriate due to different
glycosilation).
Faithfully,
Milos Zarkovic, MD, PhD
Associate Professor of Endocrinology
Milos Zarkovic
Institute of Endocrinology
Dr Subotica 13
11000 Belgrade
Yugoslavia
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The following message was posted to: PharmPK
Dr. Zarkovic,
There are mathematical models for endocrine systems which differ
from the standard pharmacokinetic equations:
Carson, E.R. et al, The Mathematical Modeling of Metabolic and Endocrine
Systems, New York, Wiley Interscience 1983
However, in a basic pharmacokinetic sense, the system you describe could
be approximated as an infusion with bolus equation:
Cp= Xoe-ket + [Ko/keVd][1-e-ket]
In the above case, the plasma levels of the endogenous LH could be fit to
this equation by nonlinear regression analysis. The infusion would represent
the basal secretion, while the bolus would represent the LH released after
the injection of the LHRH.
Another possibility is to model the plasma levels as a first order release
process after the LHRH injection, while the basal secretion could still be
modeled as an infusion:
Cp= [kaFD/(ka-ke)Vd][e-ket - e-kat] + [Ko/kdVd][1-e-ket]
The plasma levels resulting from basal secretion could be subtracted from
those measured following the LHRH bolus to remove the second term from the
above equation, and simplify the fitting process.
Using equations similar to any of the above, the Ke and T1/2 for LH could
be obtained from fitting the selected model to the observed plasma levels.
However,
the mathematical model for insulin secretion as described in Carson et al
differs
considerably from this basic pharmacokinetic analysis.
Mike Leibold,
PharmD, RPh
ML11439.at.goodne
ML11439.at.goodnet.com
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)