The pharmacokinetics and pharmacodynamics of PF-00734200, a DPP-IV inhibitor, in healthy Japanese subjects

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. Materials and 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. Scrum 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 similar to 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 similar to 75%. Conclusion: Pharmacokinetics of PF-00734200, inhibition of DPP-IV, and non-linear increases in GLP-1 were similar between healthy Japanese and Western subjects.