I think there is no difference between simultaneous administration or
not as the dose is directed to the appropriate compartment using CMT
variable. In any case two dosing records (one for each drug) are needed,
and the relative times of these records are not important. So it is
exactly like two models (one for each drug) written in one control
stream (with different compartments used for each drug). CMT is used to
direct the dose. DVID or CMT can be used to identify observations for
each drug. Interactions can be studied using correlations of random
effects, or using joint parameters, or directly specifying how
concentration of one drug influences the parameters of the other drug.
Regards,
Leonid
On 9/2/2016 3:01 PM, William Denney wrote:
Hi Chris,
I think that the most straight-forward way to handle this is to have two
sets of compartments and write the $DES block manually (or writing the
algebraic equations if it's a one- or two-compartment model).
It wouldn't be straight-forward to model if the subjects receive the
drugs at the same time. If the drugs are received at separate times
(like different periods of a study or even different studies), then the
DVID flag idea would work, too.
There are only five EVID values as far as I know, and there's not a
subtle way to use them for two doses, I don't think:
• 0= observation
• 1= dose
• 2= other (I usually use it to reset the compartment)
• 3= reset the subject
• 4= reset and dose at the same time
Thanks,
Bill
On Sep 2, 2016, at 1:22 PM, Penland, Chris
<chris.penl...@astrazeneca.com <mailto:chris.penl...@astrazeneca.com>>
wrote:
Greetings NMusers,
Does nonmem have the capacity, unbeknownst to me, for modeling two
simultaneous drugs?
I would like some suggestions about how to define the dataset and
model for a subcutaneous drug and oral drug being administered on
different schedules. I would use DVID = 1 and 2 for the two plasma pk
observations. I figure this soft of thing had to be dealt with in the
past when trying to model dynamic DDIs (vs, just taking one of the
drugs as a covariate on the other’s parameters).
One approach is to specify the compartments for each to be dosed into
then have those feed the central, but I’m curious to see if there is
something more subtle in the nonmem syntax. Is there something about
EVID, that I don’t know that would help (beyond EVID=1 for dosing)
What if you had two oral drugs? Would you treat the two dosing
compartments as separate and possibly link them together at the
parameter/covariance level?
Thanks,
Chris
Chris Penland, PhD
ECD / Quantitative Clinical Pharmacology
Waltham, MA USA
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