Re: 70kg neonates

From: Nick Holford <n.holford@auckland.ac.nz> Subject: Re: 70kg neonates Date: Fri, 06 Jul 2001 00:01:31 +1200 Leon, Leon Aarons wrote: > > Nick encouraged me to post an issue about normalising pk data for > neonates. He said he would then reply (why do I think I am being set > up?) <grin> > Anyway in Brian Anderson's paper, which Nick refers to, several pk > parameters are adjusted to 70kg. I hesitate to use the word > normalisation (and particularly not centring/centering see below for > my other concerns about this) since I am not sure what is normal > here. My concern about Brian's use of 70kg (and it is not a major > one) is that although it allows quick comparison of neonate pk to > adult pk, it does have the potential to confuse some readers when > they want to compare values between studies. Per kg is widely used > and achieves the same aim as per 70kg. I simply feel iit is more > "legible". That is all. Prediction of CL from weight using a value reported per kg depends on the model. If you use the simple per kg scaling model then this flies in the face of a large amount of empirical biological observation and some quite elegant theory (see the Br J CLin Pcol paper for references). While I accept it might be easier to multiply by weight instead of multiplying by weight^(3/4) (as experiment and allometric theory would recommend) why bother if the answer is wrong? The "legible" direct comparison of clearances calculated using the per kg model in adults and children has caused many to claim that clearance is more rapid in children because the parameter value per kg is larger in children. This naive interpretation is readily explained by the use of the wrong model for accounting for size. It is naive because it confuses the parameter (standardised per kg) with an undefendable model. Comparison of values estimated using an allometric model (whether standardized per kg or per 70 kg) indicates that once children have grown out of the early infant stage they are simply small adults (from a pharmacokinetic perspective). > Now to my real concern: what is the spelling of centering/centring. > As usual I consulted the Oxford English Dictionary and as usual I am > more confused after doing that than before. In the extracts below you > will find three different spellings of it. I particularly like > centreing. Take your pick. I'd like to pick the first (centring) because 1) it is the oldest 2) ATTERBURY applied it to to prophesy which is the purpose that I wish to use centring. 3) The definition deals with convergence which centring is thought to speed up. Nick -- Nick Holford, Divn Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556 http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm