title: Low-dose factor VIII infusion in Chinese adult haemophilia A patients: pharmacokinetics evidence that daily infusion results in higher trough level than with every-other-day infusion with similar factor VIII consumption.
abstract: BACKGROUND
  Pharmacokinetics (PK) modelling suggests improvement of trough levels are achieved by using more frequent infusion strategy. However, no clinical study data exists to confirm or quantify improvement in trough level, particularly for low-dose prophylaxis in patients with haemophilia A.
  
  
  OBJECTIVE
  To provide evidence that low dose daily (ED) prophylaxis can increase trough levels without increasing FVIII consumption compared to every-other-day (EOD) infusion.
  
  
  METHODS
  A cross-over study on 5 IU kg-1FVIII daily vs. 10 IU kg-1EOD infusions, each for 14 days was conducted at the PUMCH-HTC. On the ED schedule, trough (immediate prior to infusion), and peak FVIII:C levels (30 min after infusion) were measured on days 1-5; and trough levels alone on days 7, 9, 11 and 13. For the EOD schedule, troughs, peaks and 4-h postinfusion were measured on day 1; troughs and peaks on days 3, 5, and 7; troughs alone on days 9, 11 and 13 and 24-h postinfusion on days 2, 4 and 6. FVIII inhibitors were assessed on days 0 and 14 during both infusion schedules.
  
  
  RESULTS
  Six patients were enrolled. PK evidence showed that daily prophylaxis achieved higher (~2 times) steady-state FVIII trough levels compared to EOD with the same total factor consumption. The daily prophylaxis had good acceptability among patients and reduced chronic pain in the joints in some patients.
  
  
  CONCLUSIONS
  Our PK study shows low-dose factor VIII daily infusion results in higher trough level than with EOD infusion with similar factor VIII consumption in Chinese adult haemophilia A patients.
authors.affiliation: Department of Hematology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China.
authors.forename: B
authors.identifier: http://orcid.org/0000-0002-1712-0768
authors.initials: B
authors.lastname: Hua
authors.affiliation: Foothills Hospital, University of Calgary, Calgary, AB, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.affiliation: Department of Hematology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Hematology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China.
authors.forename: K
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Hematology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Foothills Hospital, University of Calgary, Calgary, AB, Canada.
authors.forename: M-C
authors.initials: MC
authors.lastname: Poon
authors.affiliation: Department of Hematology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D002681:China; D004305:Dose-Response Relationship, Drug; D005169:Factor VIII / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D006467:Hemophilia A / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D005169:Factor VIII
keywords: daily; factor VIII; haemophilia; pharmacokinetics; prophylaxis; trough level