title: Single- and multiple-dose pharmacokinetics of tofacitinib in healthy Chinese volunteers.
abstract: Tofacitinib is an oral Janus kinase inhibitor. The objective of this phase 1, open-label study was to characterize the single- and multiple-dose pharmacokinetics (PK) of tofacitinib in 12 healthy, adult Chinese volunteers. Eligible subjects received oral tofacitinib 10 mg once daily on days 1 and 6 and twice daily on days 2-5. Blood samples were collected on day 1 predose and over 24 hours postdose (day 2 predose), predose on days 3-6, and over 12 hours postdose on day 6. PK parameters were calculated using noncompartmental analysis. Mean concentration-time profiles for days 1 and 6 were similar, with median time to peak concentration of 0.5 hours on both days. Plasma concentrations declined rapidly following attainment of peak concentrations, with a mean terminal half-life of 3.3 hours on day 1 (single dose) and 2.5 hours on day 6 (multiple dose). No accumulation in plasma occurred with twice-daily administration: accumulation ratio of 1.04. The rapid absorption, elimination, and systemic exposures (peak and area under the concentration-time curve) observed in healthy Chinese volunteers in this study are similar to those previously reported in white subjects.
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Sriram
authors.initials: S
authors.lastname: Krishnaswami
authors.affiliation: Pfizer Inc, Shanghai, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Christine W
authors.initials: CW
authors.lastname: Alvey
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Checchio
authors.affiliation: Pfizer Inc, Cambridge, MA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Peterson
authors.affiliation: Pfizer Inc, Shanghai, China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Riese
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D002681:China; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D000075242:Janus Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D000075242:Janus Kinase Inhibitors; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib
keywords: China; Janus kinase inhibitors; healthy volunteers; pharmacokinetics; tofacitinib