Pharmacokinetics of netilmicin in hypertonic hemodiafiltration and standard hemodialysis

Recently, we developed a peculiar model of hemodiafiltration (HDF), in which a conventional acetate hemodialysis (HD) is combined with a high flux dialyzer, a high ultrafiltration flow rate and a postdilution hypertonic reinfusion (H HDF). The pharmacokinetics of netilmicin (N), a relatively new aminoglycoside, were evaluated during 5 sessions of H HDF of 180 min and 2 sessions of HD of 270 min in the same 8 patients with a comparable blood (approximately 400 ml/min) and dialysate flow rate (approximately 520 ml/min). Additional studies were performed in 7 out of the 8 patients after 2 sessions of H HDF and one session of HD. N clearance, calculated both as plasma water and total body clearance, was so exceedingly higher during H HDF than during HD, that the amount of drug removed by H HDF in 180 min was still significantly higher than that removed by HD in 270 min. Consequently, the N half-life during HD was about 5 h, whereas during H HDF it was less than 2.5 h, approaching that reported in normal subjects. N half-life out of dialysis treatments was about 55 h. In conclusion, N pharmacokinetics are strikingly different between H HDF and HD, with N clearance during H HDF about the double of that during HD. The implications of this study are: a different dosage adjustment of aminoglycosides is needed for patients routinely treated by HDF; HDF may be a very effective treatment for the overdose of many drugs.