From: "Frederike  Lentz"
Subject: [NMusers] allometric scaling 
Date: Mon, October 18, 2004 4:32 am 

Dear NONMEM-users,

some time ago there has been a discussion about the allometric scaling of
clearance and volume of distribution according to body weight. I would like
to ask one additional question concerning this topic. 

We have a patient group of exclusively preterm infants (gestational age: 24
 35 weeks) who were treated in their first month of life. The drug is
mostly renally excreted. Would you consider the allometric model to be a
priori correct already for this population?

Thank you for any comments,


From: "Nick Holford"
Subject: RE: [NMusers] allometric scaling 
Date: Mon, October 18, 2004 4:47 am 


YES --  I would consider allometric scaling of clearance and volume to be the
correct model a priori to account for differences between the infants due to size. 

I would then look for developmental changes in renal function related to
post-gestational age and changes in volume related to post-natal age. This is
because I expect renal function will increase with age but volume (per kg) is
unlikely to change much in utero. However, after birth most babies lose a lot of
body water and this can cause substantial decreases in volume especially for drugs
with Vd closely linked to body water volume e.g. aminoglycosides.

Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand tel:+64(9)373-7599x86730 fax:373-7556