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]
NMusers: Population PK model dose in mg/m2
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.
Quoted reply history
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