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I was wondering if you knew more information regarding dosing of
Isoniazid in neonates. I've found that currently, infants are dosed
15mg/kg, children are dosed 10mg/kg, and adults are dosed 5mg/kg. Why
are infants dosed a higher concentration? How can I find what the
volume of distribution for isoniazid in neonates are? Can I still use
the lit. volume of .67L/kg?
How would I take hepatic function and renal function into consideration
for a neonate?
Thanks.
Janet Nguyen
UCSF School of Pharmacy
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The following message was posted to: PharmPK
Dear Janet,
Let me tell you two general principles for dosing in children.
First of all, neonates have blood volume per kg significantly higher
than
adults. (80 mL/kg vs. 50mL/kg (?)) Secondly, children's CYP450 metabolic
activity is in general equal or greater than that of adults.
I hope this helps.
Sunny Chapel, Ph.D.
PK Scientist
Biopharmaceutics/DMPK
Aventis Pharmaceuticals
Tel) 908-231-4375
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The following message was posted to: PharmPK
Janet,
Janet Nguyen wrote:
>
> PharmPK - Discussions about Pharmacokinetics
> Pharmacodynamics and related topics
>
> I was wondering if you knew more information regarding dosing of
> Isoniazid in neonates. I've found that currently, infants are dosed
> 15mg/kg, children are dosed 10mg/kg, and adults are dosed 5mg/kg. Why
> are infants dosed a higher concentration?
The DOSE per kg can appear to be higher in children because of the use
of an inappropriate scaling model for clearance. Note does not
necessarily mean that the CONCENTRATION target is higher in infants.
> How can I find what the
> volume of distribution for isoniazid in neonates are? Can I still use
> the lit. volume of .67L/kg?
>
Allometric scaling of volume on a per kg basis is usually fine for
prediction from adult to child values. The only caution is in neonates
who tend to have bigger volumes because they have a lot of extra water
per kg.
> How would I take hepatic function and renal function into consideration
> for a neonate?
Hard to do immediately after birth (maternal creatinine load interferes
with prediciton of CLcr in neonates using Scr). Hepatic and renal
function are typically 25-50% of that seen in adults when scaled
allometrically. Developmental maturation usually reaches adult values
by 6 months.
Nick
Nick Holford, Divn Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
email:n.holford.-at-.auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
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The following message was posted to: PharmPK
Sunny,
> Secondly, children's CYP450 metabolic
> activity is in general equal or greater than that of adults.
Do you have any scientific evidence for this assertion apart from the
common mistaken interpetation of higher mg/kg doses in children based
on unsupportable allometric scaling models?
See this reference for details of size myths:
Anderson BJ, McKee D, Holford NHG. Size, myths and the clinical
pharmacokinetics of analgesia in paediatric patients. Clinical
Pharmacokinetics 1997;33:313-327
Nick
Nick Holford, Divn Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
email:n.holford.-at-.auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
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