- On 28 May 2001 at 20:28:20, "Milos Zarkovic" (mzarkov.-a-.EUnet.yu) sent the message

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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 - On 15 Jun 2001 at 20:04:30, Michael Leibold (ML11439.-at-.goodnet.com) sent the message

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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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