Equivalent Sink and Source Constraints

When are the parameter estimates from the noncompartmental model equal to those from a linear, constant-coefficient compartmental model As DiStefano and Landaw (22) explain, they are equal when the equivalent sink and source constraints are valid. The equivalent source constraint means that all 

As previously described, if used, it will underestimate certain pharmacokinetic parameters. On the other hand, the multicompartmental model shown on the right can account for sites of loss from nonaccessible compartments, providing a richer source of information about the drug s disposition. 

Recovering Pharmacokinetic Parameters from Compartmental Models 

Assume a linear, constant-coefficient compartmental model in which compartment 1 is the accessible compartment into which the drug is administered and from which samples are taken. Following a bolus injection of the drug, the volume Vi will be estimated as a parameter of the model. Vi thus will correspond to Va for the noncompartmental model. The clearance rate from compartment 1, CLi, is equal to the product of Vi and A oi  

If the only loss is from compartment 1, then kQi equals ke, and one has 

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Similar results hold for the constant infusion or generic input. In other words, the parameters can be shown to be equal if the equivalent sink and source constraints are valid. Again, the interested reader is referred to Cobelli and Toffolo (3) or Coveil et al. (4) for details and for consideration of the situation in which the equivalent source and sink constraints are not valid. 

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