title: A Single-Dose, Open-Label Study of the Pharmacokinetics, Safety, and Tolerability of Lisdexamfetamine Dimesylate in Individuals With Normal and Impaired Renal Function.
abstract: Lisdexamfetamine (LDX) and D-amphetamine pharmacokinetics were assessed in individuals with normal and impaired renal function after a single LDX dose; LDX and D-amphetamine dialyzability was also examined.
  
  
  
  Adults (N = 40; 8/group) were enrolled in 1 of 5 renal function groups [normal function, mild impairment, moderate impairment, severe impairment/end-stage renal disease (ESRD) not requiring hemodialysis, and ESRD requiring hemodialysis] as estimated by glomerular filtration rate (GFR). Participants with normal and mild to severe renal impairment received 30 mg LDX; blood samples were collected predose and serially for 96 hours. Participants with ESRD requiring hemodialysis received 30 mg LDX predialysis and postdialysis separated by a washout period of 7-14 days. Predialysis blood samples were collected predose, serially for 72 hours, and from the dialyzer during hemodialysis; postdialysis blood samples were collected predose and serially for 48 hours. Pharmacokinetic end points included maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve from time 0 to infinity (AUC0-∞) or to last assessment (AUClast).
  
  
  
  Mean LDX Cmax, AUClast, and AUC0-∞ in participants with mild to severe renal impairment did not differ from those with normal renal function; participants with ESRD had higher mean Cmax and AUClast than those with normal renal function. D-amphetamine exposure (AUClast and AUC0-∞) increased and Cmax decreased as renal impairment increased. Almost no LDX and little D-amphetamine were recovered in the dialyzate.
  
  
  
  There seems to be prolonged D-amphetamine exposure after 30 mg LDX as renal impairment increases. In individuals with severe renal impairment (GFR: 15 ≤ 30 mL·min·1.73 m), the maximum LDX dose is 50 mg/d; in patients with ESRD (GFR: <15 mL·min·1.73 m), the maximum LDX dose is 30 mg/d. Neither LDX nor D-amphetamine is dialyzable.
authors.affiliation: *Department of Clinical Pharmacology & Pharmacokinetics; †Departments of Clinical Pharmacology & Pharmacokinetics, and Biostatistics, Shire, Lexington, Massachusetts; ‡Clinical Pharmacology of Miami, Inc.; and §Orlando Clinical Research Center, Florida.
authors.forename: James
authors.initials: J
authors.lastname: Ermer
authors.forename: Mary
authors.initials: M
authors.lastname: Corcoran
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lasseter
authors.forename: Thomas
authors.initials: T
authors.lastname: Marbury
authors.forename: Brian
authors.initials: B
authors.lastname: Yan
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Martin
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D003913:Dextroamphetamine / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects; D000069478:Lisdexamfetamine Dimesylate / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000097:blood*
chemical_list: D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine