The Wagner-Nelson method estimates the absorption rate constant, k_a, for drugs administered without assuming zero- or first-order absorption.

Its mathematical formula is derived from the mass balance equation.

A semilog plot of the percent drug unabsorbed and time can help derive k_a from the slope of the line.

However, the Wagner-Nelson method is complex and applicable only to drugs with one-compartment kinetics.

Additionally, one must know the elimination rate constant from data collected post-intravenous administration.

Alternatively, the Loo-Riegelman method estimates k_a by comparing plasma concentration-time profiles post-administration.

It uses deconvolution methods to understand relative bioavailability and absorption characteristics.

So, it provides more comprehensive data, unlike the Wagner-Nelson method, even with drugs exhibiting multicompartment characteristics.

However, similar to the Wagner-Nelson method, the Loo-Riegelman method shows limitations of intrasubject variability between administration routes. It also assumes that the drug distribution and elimination kinetics remain the same between doses.