Clearance of imipenem/cilastatin in acute renal failure patients treated by continuous hemodiafiltration (CAVHD)

In patients with acute renal failure, who were treated with continuous arteriovenous hemofiltration (CAVH) or continuous arteriovenous hemodiafiltration (CAVHD), we measured clearance rates of imipenem and cilastatin (Tiënam-500^®). Literature data on volume of distribution and on the endogenous clearance in normals and in anuric patients and the observed clearance rates by CAVH/CAVHD were used to develop guidelines for dose adaptations. Based on the desired peak levels of imipenem, normal subjects should receive the fixed imipenem/cilastatin dose combination (500 mg/500 mg) q.i.d. and patients with acute renal failure should receive the same dose b.i.d. After starting treatment with either CAVH, CAVHD or continuous venovenous hemofiltration (CVVH), no further dose adjustment is necessary. The non-renal clearance rate of cilastatin is very low compared to that of imipenem. If a patient develops anuria, the clearance rate of imipenem decreases from the normal value of 245 ml/min to 116 ml/min. Clearance rate of cilastatin, however, decreases from 230 ml/min to 3 ml/min. Therefore, in patients with renal failure accumulation of cilastatin will occur. On the other hand, if the patient is treated by CAVHD, the relative contribution of the dialyser clearance to the total drug clearance is much greater for cilastatin than for imipenem. As a result, the accumulation of cilastatin is reversed. During treatment by CAVHD, the clearance rate of imipenem raises 15%-25% and that of cilastatin 335%-600%. For this reason, we conclude that the use of the fixed dose combination (500 mg/500 mg) b.i.d. in patients with acute renal failure treated by CAVHD may be justified.