title: Pharmacokinetics of teriparatide after subcutaneous administration to volunteers with renal failure: a pilot study.
abstract: OBJECTIVE
  Teriparatide acetate was developed in the form of a synthetic analogue of the Nterminal peptide (1-34) of human parathyroid hormone for the treatment of osteoporosis; it is administered subcutaneously once weekly. However, it is not known whether the pharmacokinetics (PK) of this drug is affected by renal impairment, and this study was conducted to look into this question.
  
  
  METHODS
  A multi-center study was conducted at six hospitals in Japan. Subjects were enrolled and grouped on the basis of renal function stratified as: normal function to mild renal impairment (estimated GFR(e-GFR): ≥ 60.0 mL/min/1.73 m2) (8 subjects), moderate impairment (eGFR: 30.0 - 59.9 mL/min/1.73 m2) (5 subjects), and severe impairment (eGFR: 15.0 - 29.9 mL/min/1.73 m2) (5 subjects). The PK parameters, blood and urine electrolytes concentrations, and safety profiles were assessed following a single subcutaneous injection of teriparatide acetate (56.5 μg as teriparatide).
  
  
  RESULTS
  The elimination half-life (t1/2) and the mean residence time extrapolated to infinity were significantly prolonged in the group with severe renal impairment (t1/2: 5.0 hours) compared with normal to mild and moderate impairment groups (t1/2: 1.5 hours and 1.2 hours, respectively). However, virtually all of the teriparatide was eliminated from the blood after 24 hours. Given that the drug is administered once weekly, it appeared highly unlikely that accumulation of the drug in the body would become a problem even with repeated administration. There were no particular problems with safety or tolerability.
  
  
  CONCLUSIONS
  In treatment with teriparatide acetate once-per week formulation, prescription at the usual dosage appears to be appropriate even in renally impaired patients.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Imai
authors.forename: Makoto
authors.initials: M
authors.lastname: Watanabe
authors.forename: Tomoe
authors.initials: T
authors.lastname: Fujita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Harada
authors.forename: Takashi
authors.initials: T
authors.lastname: Moritoyo
mesh_terms: D000368:Aged; D050071:Bone Density Conservation Agents / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D051437:Renal Insufficiency / Q000378:metabolism*; D019379:Teriparatide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D050071:Bone Density Conservation Agents; D019379:Teriparatide