Elimination kinetics of plasma exchange

Abstract

Interest in the therapeutic use of plasma exchange for various diseases is growing. The two different effects of plasma exchange are elimination and activation. The kinetics are linear for elimination by plasma exchange, but not for activation. Plasma exchange is performed intermittently and can be described by intermittent kinetics. According to intermittent kinetics, plasma exchange removes 50% to 75% of a substance in plasma within 1-2 h, corresponding to an elimination half-life of 30-40 min. Hybrid kinetics, a mixture of actually intermittent but theoretically continuous elimination by plasma exchange, can however also be applied. Hybrid kinetics are more convenient and more reliable than intermittent kinetics. This is because hybrid kinetics are based solely on the concentrations before each plasma exchange; hybrid kinetics also reflect removal from the entire body and not just from the plasma compartment. According to hybrid kinetics, the amount of a substance in the body removed within 3-4 days is 50% of the difference between the initial and the final plasma concentration, depending on the intensity of plasma exchange. The intensity may well contribute at least in part to the beneficial effect of plasma exchange in various diseases.

Drug Removal by Plasmapheresis: An Evidence‐Based Review

“…However, the decrease in mean ± SD normalized area under the concentration-time curve from 1508.7 ± 513.2 to 1124.6 ± 406.3 µg/ml•hour (p≤0.05) lead some authors to suggest the necessity of replacement doses. 3,6 Because aspirin exhibits Michaelis-Menten saturation kinetics, patients with steady-state concentrations at the ascending portion of the concentration-time curve may have substantial decreases in serum salicylate concentrations during plasma exchange. 31 The aforementioned study was limited by the lack of a rebound evaluation after plasma exchange, the reliance on an extrapolated midpoint concentration to calculate clearance with plasma exchange, and the atypical use of hetastarch rather than albumin as a replacement fluid with the attendant dramatic changes in Vd.…”

“…An example is the removal of circulating autoantibodies to cholinesterase with plasma exchange, an effect that prolongs the action of anticholinesterase drugs. 6 In general, drugs with a low volume of distribution (Vd) and/or a high rate of protein binding are most likely to be removed during plasma exchange. Some have proposed that plasma exchange is useful only when plasma protein binding of a substance is greater than 80% and when the Vd is less than 0.2 L/kg.…”

“…8,9 Of note, removal of drugs with plasma exchange might be compared to the removal of immunoglobulin M; however, this suggestion was validated in only one report. 6 These 30-year-old prevailing concerns about drug removal by plasma exchange have not translated into an extensive repository of published research. Only about 70 publications-mostly case reports of overdose or exploratory ingestions-are available.…”

Immunoadsorption with tryptophan columns: A therapeutic option for the treatment of rheumatoid arthritis with septic complications

“…Although the mechanism of action can be different for the specific ligands, the immediate therapeutic effect of *Correspondence to: Andreas Schwarting, Division of Nephrology, Rheumatology and Clinical Immunology, Department of Internal Medicine, Johannes-Gutenberg University, D-55131 Mainz, Germany. E-mail: aschwart@uni-mainz.de immunoadsorption remains the same; the selective elimination of immunoglobulins without removal of other, nonpathological, plasmatic factors, thus avoiding the drawbacks of conventional plasma exchange [2].…”

“…Hydrophobic amino acids, staphylococcal protein A, dextran-sulfate, peptide ligands, and plasma complement factor C1 are examples of materials used in immunoadsorption. Although the mechanism of action can be different for the specific ligands, the immediate therapeutic effect of immunoadsorption remains the same; the selective elimination of immunoglobulins without removal of other, nonpathological, plasmatic factors, thus avoiding the drawbacks of conventional plasma exchange [2].…”