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Calculation of Absorption Rate Constants for Drugs with Incomplete Availability

1973; Elsevier BV; Volume: 62; Issue: 2 Linguagem: Inglês

10.1002/jps.2600620208

1520-6017

Donald Perrier, Milo Gibaldi,

Protein purification and stability

The absorption rate constant of a drug as determined by the Wagner–Nelson or Loo–Riegelman method, by nonlinear least-squares regression analysis, or by the method of residuals is in error when drug removal from the absorption site is due not only to absorption but also to other competing processes resulting in reduced availability, regardless of the kinetics of such processes. These methods overestimate the true absorption rate constant, the degree of overestimation increasing with decreasing bioavailability. Accordingly, calculation of absorption rate constants from plasma drug concentration–time data by commonly employed methods cannot be performed with any degree of confidence unless the drug is known to be completely absorbed as such.