Pharmacokinetics and pharmacodynamics of liposomal mifamurtide in adult volunteers with mild or moderate renal impairment

Aims To evaluate the pharmacokinetics and pharmacodynamics following a single dose of liposomal mifamurtide ( L ‐ MTP‐PE , MEPACT ®) in adult subjects with mild (calculated creatinine clearance [ CL cr ] of 50–80 ml min −1 ) or moderate ( CL cr 30–50 ml min −1 ) renal impairment in comparison with age‐, weight‐ and gender‐matched healthy subjects with normal renal function ( CL cr >80 ml min −1 ). Methods Subjects received a 4 mg dose of liposomal mifamurtide via 1 h intravenous infusion. Blood samples were collected over 72 h for analysis of plasma pharmacokinetics of total and non‐liposome‐associated (free) mifamurtide and assessment of pharmacodynamics (changes in serum interleukin‐6 [ IL ‐6], tumour necrosis factor‐α [ TNF ‐α], C ‐reactive protein [ CRP ]). Results Thirty‐three subjects were enrolled: nine with mild renal impairment, eight with moderate renal impairment and 16 healthy subjects. Geometric mean (% CV ) AUC inf for total mifamurtide was 89.5 (58.1), 94.8 (27.8), 85.1 (29.0), 95.4 (18.1) n m  h in the mild renal impairment, mild‐matched healthy subject, moderate renal impairment and moderate‐matched healthy subject groups, respectively. Mifamurtide clearance was not correlated with CL cr , estimated glomerular filtration rate or iohexol clearance (all r 2 < 0.01). AUC inf of free mifamurtide was similar across the renal function groups. There were no readily apparent differences in serum pharmacodynamic effect parameters (baseline‐adjusted AUEC last for IL ‐6 and TNF ‐α and E max for CRP ) between the renal function groups. No subjects reported grade ≥3 or serious adverse events. Conclusions Mild or moderate renal impairment does not alter the clinical pharmacokinetics or pharmacodynamics of mifamurtide. No dose modifications appear necessary for these patients based on clinical pharmacologic considerations.