Exponential tails of drug disposition curves: reality or appearance?

Since plasma drug concentration-time curves, C(t), can be examined only over a limited time range, it is unclear whether they have an exponential or power-law tail. An answer to this question is important because of the necessary extrapolation beyond the observation period (to infinity). Based on renewal theory, the present analysis shows that due to the recirculation process drug disposition curves become exponentially tailed also when the underlying organ transit time distributions have a power tail with exponent of -2 or smaller. Possible exceptions are drugs like amiodarone with anomalous distribution kinetics (deep tissue trapping) which are characterized by a power-law tail and an apparent lack of equilibrium distribution, corresponding to a fractional-in-time derivative formulation of kinetics.