Adsorption of psychotherapeutic drugs with various types of dialytic membranes

Abstract

Analyses were conducted of the adsorption phenomena of psychotherapeutic drugs in dialytic membranes, with the aim of determining whether dosage modification was necessary according to various types of dialyzers and filters.
The 7 subject pharmaceutical products used in the study were sodium valproate (SV), zonisamide (ZS), phenobarbital (PB), phenytoin sodium (PT), nitrazepam (NZ), diazepam (DP) and flutoprazepam (FP), and the membranes used were polyacrylnitrile (PAN), ethylene vinyl alcohol (EVA), polymethylmethacrylate (PMMA), polysulfone (PS) and cellulose triacetate (CA). In the in vitro experiment, adsorption of the products by the dialytic membranes was carried out at 37±1°C for 3 hours, and the following findings were obtained; SV was adsorbed by the PS membrane; FP by the PS, PMMA and CA membranes; NZ by the PS, PMMA and CA membranes; DP by the PMMA and CA membranes; PB by the CA membrane; ZS by the PS, EVA, PMMA and CA membranes; and PT by the PMMA membrane. High levels of adsorptive phenomena were observed in each case.
An experiment on the circulation of solutions of NZ, ZS and PT using dialyzers was conducted to assess the adsorption of these products by the dialytic membranes. After 30 minutes exposure, NZ adsorption returned to near normal levels in every membrane, and no phenomenon of product separation was subsequently seen in the membranes.
Upon exposure to ZS, 45%-96% adsorption was confirmed in every membrane after 1 minute, and further adsorption was observed in the PAN and PMMA membranes. Similarly, upon exposure to PT, adsorption was recognized in every membrane after 1 minute, and again, further adsorption was observed in the PMMA and CA membranes.
Following the above experiment, an observational study of the movement of these products was conducted using various dialytic membranes in patients who were taking NZ, PT, DP and SV. As a result, an adsorptive level of NZ of approximately 20%, or more, was observed in the PMMA, CA and PS membranes during 3 hours of dialysis.
No adsorption of DP was observed in the PS and CA membranes after 15 minutes. With PT and SV, adsorption levels exceeding 30% and 20%, respectively, were confirmed in the PS membrane during 3 hours of dialysis.
As the results of this study indicate that products such as NZ, SV and ZS were eliminated ectosomatically through adsorption by dialytic membranes, the use of the aforementioned products during dialysis must be carefully examined in terms of ectosomatic elimination along with other problems related to dialysis and filtration.