title: Pharmacokinetics and pharmacodynamics of tonapofylline in subjects with severe renal impairment and in elderly subjects.
abstract: OBJECTIVE
  The study was conducted to characterize the pharmacokinetics and pharmacodynamics of tonapofylline in subjects with severe renal impairment and in elderly subjects.
  
  
  METHODS
  Subjects with severe renal impairment were matched demographically with healthy subjects. Elderly subjects with normal renal function for their ages were also enrolled. All subjects (n = 8 per group) received a single intravenous administration of tonapofylline at 1 mg/kg.
  
  
  RESULTS
  The pharmacokinetics of tonapofylline was not significantly different in subjects with severe renal impairment, or in elderly subjects, as compared to healthy subjects. Among all pharmacokinetic parameters, the only statistically significant difference was observed for Cmax between the healthy and the severe renal impairment groups, which was 21% and considered clinically insignificant. Pharmacodynamic assessment demonstrated the natriuretic effects of tonapofylline across groups, with little accompanying kaliuresis. No change in renal function occurred after single dose of tonapofylline, despite substantial increases in excretion of urinary sodium. Single 1 mg/kg intravenous administration of tonapofylline was generally safe.
  
  
  CONCLUSIONS
  The pharmacokinetics of tonapofylline in subjects with severe renal impairment and elderly subjects with normal renal function for age is similar to that in healthy subjects. It has been demonstrated in all groups that tonapofylline has natriuretic effects and is able to maintain renal function, which can be beneficial to patients with congestive heart failure.
authors: Biogen Idec Inc., Cambridge, MA, USA.
authors: Z
authors: Z
authors: Li
authors: C
authors: C
authors: Tenhoor
authors: T
authors: T
authors: Marbury
authors: S
authors: S
authors: Swan
authors: Y
authors: Y
authors: Zhu
authors: B
authors: B
authors: Ticho
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000378:metabolism*; D014970:Xanthines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; C505954:BG 9928; D014970:Xanthines