Some Consequences of Drug Choice and Dosage Regimen for Patients with Impaired Kidney Function

Abstract

The object of this article is to discuss difficulties in extrapolating the performances of a drug for which the kinetic parameters are derived in healthy volunteers, to patients with severely impaired kidney function. The theoretical background of some actual or probable background is given, and a possible solution for these problems is offered, that is, choosing another drug from the same drug group. In patients without kidney function, metabolism is the only pathway of elimination. When the elimination of the metabolite formed occurs by means of renal excretion only, this metabolite accumulates in patients with impaired or absent kidney function. When a metabolic pathway of the parent drug is part of a metabolic equilibrium, the metabolic return reaction results in an “apparent parent compound,” with a half-life identical to that of the accumulated metabolite. In this way, the concentration of the “apparent” parent compound increases and the half-life of the sum of parent and “apparent” parent drug will change. Examples of this drug behavior are given for sulfamethoxazole, sulfametrole, sulfamethizole, procainamide, and N4-acetylprocainamide.