Tausif,
Using mg/m2 as the dose will lead to a misspecified scaling model for
size on clearance and volume because these two parameters do not scale
the same way with BSA. Clearance is approximately scaled OK with BSA but
volume is not (Holford 1996). You should make every effort to use the
actual dose.
If you have BSA recorded for some patients then use that to calculate
the actual dose.
If BSA is missing and you have weight then you can approximate the BSA
from 1.73*(weight/70)**0.67 and use that value of BSA to predict the
actual dose.
If weight is missing as well then use the median BSA to calculate the
actual dose and median weight to impute the weight.
With the actual dose and weight (or best guess as above) you can then
use theory based allometry to correctly scale clearance and volume to
account for differences in body size.
I would certainly recommend using both day and day 5 concs. I would
prefer to code all the doses (or use ADDL) rather than make the
assumption that you are at steady state on day 5.
Nick
Holford NH. A size standard for pharmacokinetics. Clin Pharmacokinet
1996; 30: 329-32.
On 21/12/2012 7:18 a.m., tausif Ahmed wrote:
Dear nmusers,
We are working on developing a population PK model for a drug which is
given intravenously. The drug dose is administered as mg/m2. I would
like to know from the esteemed members if we can input the dose as
mg/m2 in the data set for NONMEM. Since we do not have Body Surface
Area (BSA) information for all the patients, please let us know if we
can use mg/m2 as the dose units.
We have both day 1 and day 5 (steady state) concentrations in
patients for this compound. Please let us know that for developing the
population PK model, whether we should use day 1 or day 5 or both
concentration data set.
Inputs from the experts will be highly appreciated.
Thanks
Tausif
Tausif Ahmed, Ph.D.
Asst. Director, Translational Research,
Piramal Healthcare Limited,
1, Nirlon Complex, off Western Express Highway,
Goregaon (East), Mumbai-400063
Email: [email protected] <mailto:[email protected]>
--
Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology, Bldg 503 Room 302A
University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53
email: [email protected]
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
