Bioequivalence and Bioavailability Forum

Dear Lhasa!

❝ what is the meaning of terminal log linear phase?

If a drug distributes only within the blood and highly perfused organs (liver, brain, muscles,…) the body is treated as a whole and a one-com­part­ment model is applied (▬▬). Mathematically one exponential term (C=C₀·ℯ^-λ_z·t ) describes the elimi­na­tion.

The elimination rate constant in NCA is mainly called ‘λ_z’, where the index ‘z’ stands for ‘the last’.

In a log-linear plot (time in linear scale, concentration in logarithmic scale) roughly after 2×t_max a linear decrease is seen.

This decrease represents the elimi­na­tion of the drug form the body (either excretion of unchanged drug, or conversion to a metabolite), and may be called the log linear phase. ‘Terminal’ means the ‘last one’ – but in a one compartment model there’s only one anyhow; so the term ‘terminal’ is a little bit redundant.

If the drug distributes from the first compartment to ‘deeper’ com­part­ment(s) additional exponential terms are needed to describe the profile (▬▬). In the log-linear plot a curved time course is noticed, where the first section describes the distri­bution from the first (central) com­part­ment to the peripheral ones (perfused to a lesser extent, e.g., fat, cartilage, or even bones). Both processes (distribution and elimination) occur simultaneously (──), the concentration profile is simply the sum of both. In the example at 9.2 hours less than 1% of drug were not distributed into the peripheral compartment and the elimination becomes pre­do­minant. After 16.2 hours the concentration curve is almost superimposable with the ‘pure’ elimi­nation (less than 1% diffe­rence). This section of the curve may by called the terminal log linear phase.

We need a good estimate of the terminal rate constant in order to calculate AUC_∞ in NCA (AUC_∞=AUC_tz+C_z/λ_z). The example used a model without any noise, but in the real world it’s quite tricky to select the ‘best’ sampling points. To get an impression about the difficulties have a look at this thread…

❝ I am new in this field.

Welcome!
Have a look at David Bourne’s “A First Course in Pharmacokinetics and Biopharmaceutics”.