title: The pharmacokinetics and pharmacodynamics of PF-00734200, a DPP-IV inhibitor, in healthy Japanese subjects.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of PF-00734200, a potent dipeptidyl peptidase-IV (DPP-IV) inhibitor, in Japanese subjects, and compare the results with those in Western subjects.
  
  
  METHODS
  Eight healthy Japanese subjects received a single dose of PF-00734200 10 mg, 100 mg, or placebo. Another 8 subjects received PF-00734200 20 mg or placebo single dose once daily for 6 days. Serum and urine PK, plasma DPP-IV activity, and plasma glucagon-like peptide 1 (GLP-1) levels were measured.
  
  
  RESULTS
  Linear pharmacokinetics was observed over the single dose range 10 - 100 mg. Following multiple-dose administration, 37.3 ± 4.33% of the unchanged PF-00734200 was excreted in the urine and renal clearance was calculated as 33.9 ± 6.56 ml/min. After the standardized meals, GLP- 1 levels increased ~ 2-fold compared with placebo, and no further increase in GLP-1 levels was observed at doses above 10 mg. The steady state DPP-IV inhibition at 24 h was ~ 75%.
  
  
  CONCLUSIONS
  Pharmacokinetics of PF-00734200, inhibition of DPP-IV, and non-linear increases in GLP-1 were similar between healthy Japanese and Western subjects.
authors.affiliation: Pfizer Global Research & Development, Pfizer Japan Inc., Tokyo, Japan. chieko.muto@pfizer.com
authors.forename: Chieko
authors.initials: C
authors.lastname: Muto
authors.forename: Haiqing
authors.initials: H
authors.lastname: Dai
authors.forename: John G
authors.initials: JG
authors.lastname: Teeter
authors.forename: Susan
authors.initials: S
authors.lastname: Johnson
authors.forename: Anne B
authors.initials: AB
authors.lastname: Cropp
authors.forename: Koji
authors.initials: K
authors.lastname: Chiba
authors.forename: Toshio
authors.initials: T
authors.lastname: Suwa
mesh_terms: D000328:Adult; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D008875:Middle Aged; D011743:Pyrimidines / Q000493:pharmacokinetics* / Q000494:pharmacology; D011759:Pyrrolidines / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D011743:Pyrimidines; D011759:Pyrrolidines; D052216:Glucagon-Like Peptide 1; C558848:gosogliptin