Effect of CP-690,550, an orally active janus kinase inhibitor, on renal function in healthy adult volunteers

J Clin Pharmacol. 2009 Apr;49(4):423-9. doi: 10.1177/0091270008330982.


CP-690,550 is a Janus kinase inhibitor being developed to prevent allograft rejection and treat several autoimmune diseases. This study examines the effect of multiple doses of CP-690,550 on renal function in healthy volunteers. Thirty-four volunteers are randomized in a 2:1 ratio in a double-blinded manner to receive CP-690,550 15 mg twice daily or placebo twice daily for 14 days. Volunteers are confined in-house to receive a controlled regimen of water intake and sodium intake of 4 to 5 g/d. The effect of CP-690,550 on glomerular filtration rate (GFR) is measured by iohexol serum clearance, effective renal plasma flow (ERPF) by para-aminohippuric acid (PAH) urinary clearance, and creatinine clearance by 24-hour urine collection on day 1 (predose) and day 15. Steady-state pharmacokinetics and tolerability are assessed. Comparing the day 15 and day 1 (predose) values shows that geometric mean ratios for iohexol serum clearance, PAH urinary clearance, and creatinine clearance are 0.995, 0.925, and 0.948, respectively. When adjusted for the corresponding placebo day ratios, the geometric mean ratios are 1.09, 0.978, and 1.05, respectively. CP-690,550 is well tolerated. These findings indicate that CP-690,550 does not affect GFR, ERPF, or creatinine clearance in healthy volunteers.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Double-Blind Method
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / pharmacokinetics
  • Iohexol / metabolism
  • Janus Kinase 3 / antagonists & inhibitors*
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / physiology
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Piperidines
  • Placebos
  • Pyrimidines / adverse effects*
  • Pyrimidines / pharmacokinetics
  • Pyrroles / adverse effects*
  • Pyrroles / pharmacokinetics
  • Renal Plasma Flow, Effective / drug effects
  • p-Aminohippuric Acid / urine


  • Immunosuppressive Agents
  • Piperidines
  • Placebos
  • Pyrimidines
  • Pyrroles
  • Iohexol
  • tofacitinib
  • JAK3 protein, human
  • Janus Kinase 3
  • p-Aminohippuric Acid