The model describes the pharmacokinetics of colistimethate (CMS, prodrug of colistin) and colistin (active moiety) in patients receiving continuous renal replacement therapy (CRRT). It was fitted to observations collected in 10 intensive care patients providing 96 pre-filter and 15 post-filter plasma samples together with 12 effluent samples for CMS and colistin determination. The systemic disposition of both molecules was described with a single compartment model, estimating the clearance and the distribution volume of each moiety. The exchanges occurring in the CRRT device were modelled according to a physiologically-inspired model extension, taking into account real blood and filtrate-dialysate flow rates, actual filter and cartridge volumes and patients' haematocrit, and estimating the sieving coefficients of CMS and colistin. The model predicts that a CMS loading dose of 9 MU followed after 8 h by a maintenance dosage of 3 MU 8-hourly will achieve therapeutic colistin concentration exposure (>2.5 mg/L over the whole dosing interval) in patients undergoing CVVHD using low blood flows.