Determination of unbound fraction of disopyramide in plasma: a comparison of equilibrium dialysis, ultrafiltration through dialysis membranes and ultrafree anticonvulsant drug filters. 1982

R L Norris, and J T Ahokas, and P J Ravenscroft

A simple, rapid ultrafiltration technique for determination of free drug concentration in plasma is described and compared with equilibrium dialysis and ultrafiltration through dialysis membranes. When used for disopyramide protein binding studies, this method requires only 1 ml of plasma and up to 20 samples may be filtered simultaneously in 20-40 min. Commercially available Ultrafree anticonvulsant drug filters are used, these are attached to 2 ml leur tip syringes, which provide the pressure gradient for filtration. Compared to equilibrium dialysis this technique is far quicker and permits protein binding to be measured at the drug concentration in the original plasma. Ultrafiltration through dialysis membranes was found to be more tedious and time-consuming than it was through Ultrafree filters. Adsorption of disopyramide from the plasma sample and protein leakage were also problems with this method. Leakage of protein did not occur with either Ultrafree filters or equilibrium dialysis. With the Ultrafree method, recovery of 14C-labeled disopyramide in buffer at 1.1 micrograms/ml and 8.4 micrograms/ml was 87% and 89% respectively. In carefully controlled experiments, a comparison of the Ultrafree method with equilibrium dialysis and ultrafiltration gave comparable values for the free fraction of the drug for total concentrations from 0.3-8 microgram/ml disopyramide.

UI MeSH Term Description Entries
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D001798 Blood Proteins Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins. Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
D003956 Dialysis A process of selective diffusion through a membrane. It is usually used to separate low-molecular-weight solutes which diffuse through the membrane from the colloidal and high-molecular-weight solutes which do not. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Dialyses
D004206 Disopyramide A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties. Diisopyramide,Disopyramide Monohydrochloride,Disopyramide Phosphate,Disopyramide Phosphate (1:1),Disopyramide Phosphate (1:1), (+-)-Isomer,Disopyramide Phosphate (1:1), (R)-Isomer,Disopyramide Phosphate (1:1), (S)-Isomer,Disopyramide, (+-)-Isomer,Disopyramide, (R)-Isomer,Disopyramide, (S)-Isomer,Disopyramide, D-Tartrate (1:1), (S)-Isomer,Disopyramide, L-Tartrate (1:1), (R)-Isomer,Disopyramide, L-Tartrate (1:1), (S)-Isomer,Disopyramide, L-Tartrate (1:2), (+-)-Isomer,Disopyramide, L-Tartrate, (S)-isomer,Norpace,Palpitin,Palpitine,Rhythmodan,Ritmilen,Rythmilen,SC-13957,SC 13957,SC13957
D005374 Filtration A process of separating particulate matter from a fluid, such as air or a liquid, by passing the fluid carrier through a medium that will not pass the particulates. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Filtrations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014462 Ultrafiltration The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in DIALYSIS separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as HEMOFILTRATION or HEMODIAFILTRATION (if combined with HEMODIALYSIS).

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