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Hello everyone.
Multiple PK books describe how to apply the method of residuals to get the rate constants for 2
compartment IV bolus drugs and for 1 compartment oral model drugs.
1-Does anyone know of a reference discussing the feasibility of applying the method of residuals to
a 2 compartment oral model drug to get ka, alpha and beta?
2- Gabrielsson and Weiner Book ( 4th ed. page 294) shows the following as the integrated form of the
equation for Cp following constant rate IV infusion of a 2 compartment drug.
Cp = (Ro/Vc) *[{(K21 - alpha) *( 1-e ^-alpha Tinf) * e ^ - alpha *(t-Tinf)}/ alpha*( beta - alpha)]
+ (Ro/Vc) * [{ (k21-beta) * (1-e^-beta * Tinf)* e^-beta*(t -Tinf)}/ beta *(alpha-beta)]
Can anyone provide the equivalent equation in macroconstant terms only ( alpha and beta)? Does K21
= (A * beta + B * alpha)/ (A+ B) similar to the IV bolus 2 comp model? If so, do we just ignore the
ascending part of the curve in estimating A and B via the method of residuals ?
what about Vc? for an IV bolus 2 comp, Vc= Dose/ K10 *AUC o to inf and AUC o to inf = (A /alpha) +
(B / beta)
Thank you very much for any feedback
Best
Noha
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