title: Pharmacokinetics and Tolerability of Exenatide Delivered by 7-Day Continuous Subcutaneous Infusion in Healthy Volunteers.
abstract: BACKGROUND
  Small peptides are approved as treatments for type 2 diabetes mellitus and may have utility in metabolic diseases. These peptides often have short half-lives requiring delivery either as a sustained-release formulation or via a device. The opportunity to study their pharmacokinetics using simple solution formulations delivered by continuous subcutaneous infusion may facilitate the drug development process.
  
  
  METHODS
  Here, we investigated the systemic exposure of an exemplar peptide (exenatide) when infused in healthy subjects using a Paradigm(®) Revel™ insulin infusion pump (Medtronic MiniMed). Four infusion regimens were tested: Constant 24-h infusion (16.5 μg/day), constant 7-day infusion (25.5 μg/day in Cohort 2), and two different 7-day escalation regimens (ranging from 7 to 58.5 μg/day in Cohort 1 and 25.5-58.5 μg/day in Cohort 3).
  
  
  RESULTS
  While the overall exenatide pharmacokinetics were in line with those expected, the observed within-subject concentration variability was considerable.
  
  
  CONCLUSIONS
  Our work identifies sources of potential pharmacokinetic variability relating to the method of delivery and the drug's formulation that will be valuable to investigators contemplating the delivery of peptides via insulin infusion pumps.
  
  
  BACKGROUND
  GlaxoSmithKline.
  
  
  BACKGROUND
  ClinicalTrials.gov number, NCT01857895.
authors.affiliation: GlaxoSmithKline Research and Development, Stockley Park West, Uxbridge, London, UB11 1BT, UK, georgios.x.vlasakakis@gsk.com.
authors.forename: Georgios
authors.initials: G
authors.lastname: Vlasakakis
authors.forename: Susan L
authors.initials: SL
authors.lastname: Johnson
authors.forename: Jiang
authors.initials: J
authors.lastname: Lin
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Yao
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Gruenloh
authors.forename: John P
authors.initials: JP
authors.lastname: Chism
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Nunez
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D000077270:Exenatide; D005260:Female; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D055104:Infusions, Subcutaneous; D007332:Insulin Infusion Systems; D008297:Male; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D014688:Venoms / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*
chemical_list: D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D000077270:Exenatide