- On 7 Nov 2005 at 10:22:43, Wayne Luther (wayneluther.-at-.gmail.com) sent the message

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Hi,

I am trying to workout the equation for multiple oral dosing in a two

compartment model using the general principle:

(Cmax)n = (ka * F * Xo / V) * ((L * (1 - exp(-n * a * t)) / (1 -

exp(-a * t))) + (M * (1 - exp (-n * b * t)) / (1 -exp(-b * t))) - (N *

(1 - exp (-n * ka * t)) / (1 -exp(-ka * t))))

(Cmin)n = (ka * F * Xo / V) * ((L * (1 - exp(-n * a * t)) * exp(-a *

t) / (1 - exp(-a * t))) + (M * (1 - exp (-n * b * t)) * exp(-b * t)/ (1

-exp(-b * t))) - (N * (1 - exp (-n * ka * t)) * exp(-ka * t) / (1

-exp(-ka * t))))

However, upon inputting my values I noticed the max values are always

lower than the min values.

Does anybody have any comments or suggestions as to why this is the

case?

Thanks in advance,

Regards,

Wayne - On 8 Nov 2005 at 19:34:04, David-Bourne.at.ouhsc.edu sent the message

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The following message was posted to: PharmPK

Dear Wayne,

There are some possible problems:

1) Your equation for Cmax does not give the maximum concentration, but

the concentration at the beginning of each dosing interval. For

intravenous dosing this is the maximum, but for extravascular dosing it

is not. Your finding that 'your Cmax' is lower than Cmin is correct,

since it is actually Cmin after the previous dose!

It is not so easy to calculate Cmax after extravascular dosing, since

one should know Tmax, which is dependent on all parameters including n.

2) It is not clear what your L, M and N refer to. If these are the

intercepts of the equation found by curve-fitting of a polyexponential

equation, the term

(ka * F * Xo / V)

should be left out.

3) The sum L + M + N should be equal to zero to satisfy the condition

that C=0 at time zero.

4) You are using N and n for different purposes; N is the intercept of

the ka-term, and n is the number of doses. This is confusing!

5) Note that t is the dosing interval, not time.

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.-a-.rug.nl

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