title: Pharmacokinetics of the Long-Acting Basal Insulin LY2605541 in Subjects With Varying Degrees of Renal Function.
abstract: The pharmacokinetics of LY2605541 (basal insulin peglispro), a novel long-acting basal insulin analogue, was evaluated in 5 groups of subjects with varying degrees of renal function based on creatinine clearance: normal renal function (>80 mL/min), mild renal impairment (51-80 mL/min), moderate renal impairment (30-50 mL/min), severe renal impairment (<30 mL/min), or end-stage renal disease (ESRD) requiring hemodialysis. Serial blood samples for pharmacokinetic analyses were collected up to 12 days following a single 0.33 U/kg subcutaneous dose of LY2605541. The apparent clearance (CL/F) and half-life across groups were not affected by renal function. Cmax values were lower in subjects with increasing severity of renal impairment; however, the small decrease in Cmax did not affect the overall exposure. Regression analysis showed that LY2605541 clearance is independent of renal function (slope = 0.000863; P = .885). The mean fraction of LY2605541 eliminated by a single hemodialysis session was 13% in subjects with ESRD. LY2605541 was generally well tolerated in healthy subjects and those with renal impairment following a single 0.33 U/kg subcutaneous dose. Given these data, no dose adjustment of LY2605541 based on pharmacokinetics is recommended in renal impairment or in patients undergoing hemodialysis.
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Helle
authors.initials: H
authors.lastname: Linnebjerg
authors.affiliation: Lilly-NUS Clinical Pharmacology Pte Ltd, Singapore.
authors.forename: Siak Leng
authors.initials: SL
authors.lastname: Choi
authors.affiliation: Lilly-NUS Clinical Pharmacology Pte Ltd, Singapore.
authors.forename: Eric Chen Quin
authors.initials: EC
authors.lastname: Lam
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Mace
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Teri S
authors.initials: TS
authors.lastname: Hodgson
authors.affiliation: U.S. Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Vikram P
authors.initials: VP
authors.lastname: Sinha
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007279:Injections, Subcutaneous; D061268:Insulin Lispro / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007676:Kidney Failure, Chronic / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D012044:Regression Analysis; D006435:Renal Dialysis / Q000379:methods; D051437:Renal Insufficiency / Q000503:physiopathology*; D012720:Severity of Illness Index
chemical_list: D007004:Hypoglycemic Agents; D061268:Insulin Lispro; C587357:LY2605541; D011092:Polyethylene Glycols
keywords: insulin peglispro; long-acting basal insulin analogue; pharmacokinetics; renal impairment