Study of factors affecting drug extraction during continuous hemofiltration and hemodiafiltration, and the contribution of extraction to systemic clearance]

The aim of this study was to elucidate the factors affecting dialysis clearance and the need for additional doses of drugs during and after continuous hemofiltration (CHF) and hemodiafiltration (CHDF). We performed a literature search of MEDLINE using the terms hemofiltration OR hemodiafiltration AND pharmacokinetics to obtain the clearances of CHF and CHDF in a clinical setting. The relationships between molecular weight, the unbound fraction (fuB), ultrafiltration flow rate (UFR) and dialysis flow rate were analyzed. The need for additional doses of certain drugs was also discussed based on the ratio of dialysis and systemic clearances. The clearance of CHF for 32 reported drugs was significantly correlated with the product of fuB X UFR (r=0.841, p<0.001), and furthermore the plots obtained lay on a line of y=x. The clearance of CHDF also showed good correlation with the product of fuB X UFR (r=0.795, p<0.001), but the plots were higher than the line for y=x, suggesting that additional clearance by dialysis was not negligible. The elimination by both forms of dialysis for drugs excreted mainly via the kidneys, and with a higher fuB, was considerable. The extent of drug clearance by both CHF and CHDF is determined mainly by fuB and UFR. The ratio of dialysis clearance to systemic clearance should be estimated to determine the contribution of CHF and CHDF.