A consistent nomenclature for describing pharmacokinetics and dialyser performance

Introduction: Since renal dialysis machines were introduced into clinical practice in the 1950s, dialysis has immensely evolved to become the core treatment for patients with end stage renal disease. However, quantifying dialysis performance and its effect on medication clearance is still challenging. The Michaels equations, often used  to calculate blood dialysance, were derived for 3 different historic dialysis systems (Michaels, 1966), including obsolete systems with parallel flow and recirculating dialysate (for which increasing dialysis bath concentration had to be taken into account when calculating dialyser performance). Michaels did not explicitly present his derivations in the paper, and it is unclear to what extent his equations are still applicable to describe modern single-pass counter-current dialysers. Moreover, over the years, the terminology in the pharmacokinetic and dialysis literature has been inconsistent and confusing, and it is challenging to understand and apply these concepts for modeling the dialysis of drugs.

Aims: To introduce a consistent and universal terminology applicable to pharmacokinetics with and without dialysis with an emphasis on modern-day dialyzers.

Methods: We reviewed the literature on the pharmacokinetics modeling of dialysis, compared the terminology and the definition of the various terms used, and used mathematical derivations to show how these terms are interconnected.

Results: We have derived the Michaels equations for both single pass and recirculating dialysers, and some challenging conundrums have emerged. We explain the term K0A (diffusion overall rate constant and dialyser surface area) and its analogy to intrinsic clearance. We defined dialysis efficiency and describe how it can be applied to modeling dialysis clearance of drugs.

Conclusion: A consistent nomenclature may be helpful in better understanding the pharmacokinetics of dialysis and modeling the dialysis of drugs.

Michaels, A. S. (1966). Operating parameters and performance criteria for hemodialyzers and other membrane-separation devices. Transactions – American Society for Artificial Internal Organs, 12, 387–392.