Evaluation of MPA and MPAG Removal by Continuous Venovenous Hemodiafiltration and Continuous Venovenous Hemofiltration

Abstract

The study assessed the removal of mycophenolic acid (MPA) and its major glucuronide metabolite (MPAG) during continuous venovenous hemofiltration (CVVHF) and continuous venovenous hemodiafiltration (CVVHDF) in 4 heart transplant recipients treated for at least 6 days with mycophenolate mofetil (MMF) in addition to cyclosporine and corticosteroids. The sieving coefficient ranged from 0.02 to 0.04 for MPA and from 0.15 to 0.33 for MPAG. The clearance of MPAG by CVVHDF or CVVHF ranged from 7.52 mL/min to 19.45 mL/min, and that of MPA was lower than 2.28 mL/min, with no significant difference between the two continuous replacement therapies. Whereas MPA percentage recovered by hour following CVVHDF or CVVHF was negligible, the percentage of MPAG represents up to 12.9% of the administered dose. A relevant decrease in the free fraction of MPA and MPAG was observed after continuous renal replacement therapy (CRRT). These preliminary results demonstrate that MPAG is able to permeate the filter. In light of the alteration in protein binding following CRRT and the competition between MPA and MPAG to albumin site, drug monitoring of MPA and MPAG in patients undergoing CVVHDF or CVVHF may be suggested. Moreover, monitoring of free MPA may be of interest for these patients.

Relationship between MPA free fraction and free MPAG concentrations in heart transplant recipients based on simultaneous HPLC quantification of the target compounds in human plasma

“…Sorption of the analytes on polypropylene containers using sodium chloride solution as solvent being previously reported [20], the same methodology was applied to the sample vial of the disposable centrifugal filter device made of polypropylene with a sodium chloride solution containing 0.1/1 mg/L of MPA/MPAG.…”

Hemofiltration and Coupled Plasma Filtration Adsorption Impact on Tacrolimus Blood Concentration in Renal Transplant Recipients

“…При этом, несмотря на то что глюкуронид фармакологической активностью не обладает, может изменяться концентрация микофеноловой кислоты в крови в результате изменения их соотношения и конкурентного связывания с альбумином. В связи с этим может потребоваться лабораторный контроль [11]. Также известно, что и гемодиализ может приводить к снижению концентрации глюкуронида микофеноловой кислоты (но не самой микофеноловой кислоты) в раннем послеоперационном периоде после трансплантации почки [12].…”