Meropenem clearance by continuous haemofiltration: a comparison of in vivo and in vitro data

Often a new drug is licensed for use in the critically ill before its pharmacokinetic profile has been fully described. In particular information relating to the amount removed by continuous renal replacement therapies, such as haemofiltration, is sparse. This relates to the difficulties associated with patient recruitment and standardisation for in vivo studies. This study describes the removal of meropenem, a broad spectrum antibiotic, by an in vitro model of haemofiltration and compares the data with that obtained in a previous in vivo investigation [1]. The in vitro model incorporated a polyacrylonitrile membrane (Hospal, Multiflow 60) employing a blood pump (Hospal BSM22SC) to circulate carrier fluid (3.5% human albumin solution in Tyrode Ringer) around an extracorporeal circuit. Ultrafiltration rates were manipulated using a peristaltic pump attached to the ultrafiltration line. Pre-membrane, post-membrane and ultrafiltration samples were collected from the model at timed intervals, employing three different UFR rates. Meropenem concentrations were measured by HPLC and used to calculate the drugs' sieving coefficient (S) and filter clearance (FCL), using standard equations [2]. The results were then compared to values obtained from a previous in vivo study [1] employing a similar membrane (Hospal, Multiflow 100). A mean (± SD) S value of 0.99 ± 0.07 (n = 13) was calculated for the in vitro model for al UFR rates used which compared favourably with a mean (± SD) S of 0.95 ± 0.03 reported during the in vivo study, involving four patients. A significant linear correlation was seen between UFR and FCL for both in vitro and in vivo data (r = 0.98, P < 0.05 and r = 0.90, P < 0.05, respectively). The results of this study suggest that the in vitro model is capable of providing accurate meropenem filter clearance data. Although further validation of this model using a range of drugs is required, this preliminary work suggests that, in the absence of in vivo pharmacokinetic information, extracorporcal drug clearance determined using an in vitro model could be used to aid prescribing in patients receiving haemofiltration.