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Pharmacokinetics of anakinra in subjects with different levels of renal function
Author(s) -
Yang BingBing,
Baughman Sharon,
Sullivan John T.
Publication year - 2003
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(03)00094-8
Subject(s) - anakinra , medicine , renal function , hemodialysis , pharmacokinetics , end stage renal disease , dialysis , creatinine , urology , dosing , pharmacodynamics , endocrinology , disease
Objective Our objective was to assess the effects of decreased renal function and dialysis on anakinra pharmacokinetics. Methods In 2 separate studies anakinra (1 mg/kg) was given intravenously to 12 healthy subjects and 20 subjects with end‐stage renal disease undergoing dialysis. In a third study anakinra (100 mg) was given subcutaneously to 30 subjects who had been assigned to 5 groups according to renal function, as follows: normal (creatinine clearance [CL cr ] >80 mL/min), mildly impaired (CL cr = 50‐80 mL/min), moderately impaired (CL cr = 30‐49 mL/min), severely impaired (CL cr <30 mL/min), and end‐stage renal disease undergoing hemodialysis. Plasma samples were collected up to 96 hours after dosing for anakinra measurement by enzyme‐linked immunoassay. Results The mean plasma clearance (CL) of anakinra after intravenous administration was reduced from 137 ± 21 mL/min in the healthy subjects to approximately 20 mL/min for the subjects with end‐stage renal disease ( P < .0001). The removal of anakinra by dialysis was less than 2.5% of the dose administered. Compared with mean anakinra clearance (CL/F) after subcutaneous administration in the group with normal renal function (170 ± 37 mL/min), CL/F was reduced by 16% in the mildly impaired group (142 ± 59 mL/min), by 50% in the moderately impaired group (84.5 ± 24.7 mL/min, P < .05), by 70% in the severely impaired group (51.5 ± 8.4 mL/min, P < .05), and by 75% in the group with end‐stage renal disease (42.7 ± 4.7 mL/min, P < .05). A significant correlation between anakinra CL/F and CL cr was observed [log(CL/F) = 1.65 + 0.0062 · CL cr ; r 2 = 0.718]. Conclusion Anakinra is predominantly cleared renally in humans; the plasma clearance of anakinra decreased with decreasing renal function. The dialysis process has a minimal effect on the removal of anakinra. Our results suggest that a dose or schedule adjustment is indicated for persons with severe renal impairment or end‐stage renal disease. Clinical Pharmacology & Therapeutics (2003) 74 , 85–94; doi: 10.1016/S0009‐9236(03)00094‐8