NONMEM Users Network Archive

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RE: Modeling Growth Hormone Pulsatility

From: Jian Xu <alanub>
Date: Fri, 30 Mar 2007 15:30:22 -0700 (PDT)

Dear Dr. Karlsson,

Thanks for your quick reply.

I have come across your paper, and read it. However, this Surge function is only able to identify one Pulse. When multiple pulses exist, it will not work unless several surge functions added (possible?), which will over-parameterize model. Please correct me if I am wrong. I am looking for an algorithm to be capable to identify multiple pulses.

Thank you again, and have a nice weekend,

Jian

Mats Karlsson <mats.karlsson
   
  We have good experience of a surge function. Surges, characterised by the parameters SA (surge amplitude), SW (surge width), T (clock time) and Pt (peak time), were used to define the function g(clock time) according to Eq. 4.
 
 g(Clock time) = SA / (((T Pt) / SW)4 + 1) (Eq.4)
   
  This was presented by Nelamangala et al below (applied to LH surges). We applied it to ACTH / Cortisol. It was superior to (sum of) cosine functions for these hormones.
   
  Best regards,
  Mats
   
  Nelamangala N, Pechstein B, Erb K, Klipping C, Hermann R, Locher M, Derendorf H. Pharmacokinetic/Pharmacodynamic modeling of luteinizing hormone (LH) suppression and LH surge delay by Cetrorelix after single and multiple doses in healthy postmenopausal women. J Clin Pharmacol 2003; 43:243-251.
   
  Lonnebo A, Grahnen A, Karlsson MO.
  An integrated model for the effect of budesonide on ACTH and cortisol in healthy volunteers.
  Br J Clin Pharmacol. 2007 Feb 28; [Epub ahead of print]
   
   
    Mats Karlsson, PhD
 Professor of Pharmacometrics
 Div. of Pharmacokinetics and Drug Therapy
 Dept. of Pharmaceutical Biosciences
 Faculty of Pharmacy
 Uppsala University
 Box 591
 SE-751 24 Uppsala
 Sweden
 phone +46 18 471 4105
 fax +46 18 471 4003
 mats.karlsson
      
---------------------------------
  
  From: owner-nmusers
 Sent: Friday, March 30, 2007 23:07
 To: nmusers
 Subject: [NMusers] Modeling Growth Hormone Pulsatility
  
   
  Dear everyone,
 
 I am looking for any reference for modeling hormone pulsatility in PK softwares.
 
 Would you recommend some good articles to me? Or any suggestion?
 
 Thanks in advance.
 
 I searched PubMed, and the Pulsatility can be modeled by some statistical models, which is not that easily to translate and implement in PK software, such as NONMEM, or ADAPT II.
 
 Jian
    
    
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Received on Fri Mar 30 2007 - 18:30:22 EDT

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