# PharmPK Discussion - Multiple Oral Dosing Two Compartment

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• On 7 Nov 2005 at 10:22:43, Wayne Luther (wayneluther.-at-.gmail.com) sent the message
`Hi,  I am trying to workout the equation for multiple oral dosing in a twocompartment 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 alwayslower than the min values.  Does anybody have any comments or suggestions as to why this is thecase?  Thanks in advance,  Regards,  Wayne`
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• On 8 Nov 2005 at 19:34:04, David-Bourne.at.ouhsc.edu sent the message
`The following message was posted to: PharmPKDear Wayne,There are some possible problems:1) Your equation for Cmax does not give the maximum concentration, butthe concentration at the beginning of each dosing interval. Forintravenous dosing this is the maximum, but for extravascular dosing itis 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, sinceone 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 theintercepts of the equation found by curve-fitting of a polyexponentialequation, the term(ka * F * Xo / V)should be left out.3) The sum L + M + N should be equal to zero to satisfy the conditionthat C=0 at time zero.4) You are using N and n for different purposes; N is the intercept ofthe 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 ProostJohannes H. ProostDept. of Pharmacokinetics and Drug DeliveryUniversity Centre for PharmacyAntonius Deusinglaan 19713 AV Groningen, The Netherlandstel. 31-50 363 3292fax 31-50 363 3247Email: j.h.proost.-a-.rug.nl`
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