Muto Chieko, Dai Haiqing, Teeter John G, Johnson Susan, Cropp Anne B, Chiba Koji, Suwa Toshio
Pfizer Global Research & Development, Pfizer Japan Inc., Tokyo, Japan.
Int J Clin Pharmacol Ther. 2012 Jul;50(7):505-9. doi: 10.5414/CP201614.
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.
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.
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%.
Pharmacokinetics of PF-00734200, inhibition of DPP-IV, and non-linear increases in GLP-1 were similar between healthy Japanese and Western subjects.
评估强效二肽基肽酶-IV（DPP-IV）抑制剂PF-00734200在日本受试者中的药代动力学、药效学、安全性和耐受性，并将结果与西方受试者进行比较。
8名健康日本受试者接受单剂量10mg、100mg的PF-00734200或安慰剂。另外8名受试者每天接受一次单剂量20mg的PF-00734200或安慰剂，共6天。测量血清和尿液药代动力学、血浆DPP-IV活性以及血浆胰高血糖素样肽1（GLP-1）水平。
在10 - 100mg单剂量范围内观察到线性药代动力学。多次给药后，37.3±4.33%的未变化PF-00734200经尿液排泄，计算得出肾脏清除率为33.9±6.56ml/min。标准化餐后，与安慰剂相比，GLP-1水平升高约2倍，在剂量高于10mg时未观察到GLP-1水平进一步升高。24小时时的稳态DPP-IV抑制率约为75%。
健康日本受试者和西方受试者在PF-00734200的药代动力学、DPP-IV抑制以及GLP-1的非线性增加方面相似。
