- On 1 Apr 2003 at 16:43:32, "Prapoch Watanalumlerd (Keng)" (watanalp.-at-.onid.orst.edu) sent the message

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The following message was posted to: PharmPK

Dear all,

Does anyone have information about the appropriate probability

distribution of

lag time of absorption (Tlag) for Monte Carlo simulations? Since Tlag

obtained

from biostudies is a discrete ordinal variable, I have difficulties

including

its variability in the simulation. Thank you.

Best Regards,

Prapoch Watanalumlerd (Keng)

Pharmaceutic graduate student

College of Pharmacy, Oregon State University

Phone: 541-737-5789 - On 2 Apr 2003 at 08:54:25, "Hans Proost" (j.h.proost.-at-.farm.rug.nl) sent the message

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The following message was posted to: PharmPK

Dear Keng,

You wrote:

> Does anyone have information about the appropriate probability

> distribution of lag time of absorption (Tlag) for Monte Carlo

> simulations?

> Since Tlag obtained from biostudies is a discrete ordinal variable,

> I have difficulties including its variability in the simulation.

For most, if not all, a log-normal distribution of PK parameters is the

logical choice (as was discussed recently in this group). I do no see a

specific reason why this would not hold for the lag time of absorption

(Tlag). IMHO, this is the logical choice in case you are using a PK

model

including a lag time. If you estimate Tlag from a series of

measurements,

the obtained value is not a discrete variable, but an estimate of the

'true'

Tlag.

Possibly you are referring to a noncompartmental approach where Tlag is

defined as the last measured time point where the concentration is zero

(or

more precisely, below the LOD, or LOQ, or whatever criterion is

defined). In

this case Tlag is indeed a discrete ordinal variable. Since the 'true'

Tlag

may still be described by a log-normal distribution, the following

approach

could be used. Given a geometric mean and standard deviation for Tlag,

the

probability that Tlag is between 0 and t1 (time of first measurement)

can be

calculated, and this is the probability that the observed Tlag is 0,

i.e.

the probability that at t1 at least some drug has been absorbed.

Similarly,

the probability that Tlag is between t1 and t2 (time of first

measurement)

equals the probability that the observed Tlag is t1 (i.e. at least some

drug

absorbed at t2), et cetera.

Any suggestions about this approach are welcomed.

Best regards,

Hans Proost

Johannes H. Proost

Dept. of Pharmacokinetics and Drug Delivery

University Centre for Pharmacy

Antonius Deusinglaan 1

9713 AV Groningen, The Netherlands

tel. 31-50 363 3292

fax 31-50 363 3247

Email: j.h.proost.-at-.farm.rug.nl

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