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Pharmacokinetics of the Long‐Acting Basal Insulin LY2605541 in Subjects With Varying Degrees of Renal Function
Author(s) -
Linnebjerg Helle,
Choi Siak Leng,
Lam Eric Chen Quin,
Mace Kenneth F.,
Hodgson Teri S.,
Sinha Vikram P.
Publication year - 2016
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.252
Subject(s) - medicine , pharmacokinetics , renal function , cmax , hemodialysis , urology , basal (medicine) , kidney disease , end stage renal disease , creatinine , kidney , endocrinology , insulin
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. C max values were lower in subjects with increasing severity of renal impairment; however, the small decrease in C max 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.