ORIGINAL ARTICLE 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 B. HUA,* A. LEE, † L. FAN,* K. LI,* Y. ZHANG,* M.-C. POON † and Y. ZHAO* *Department of Hematology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China; and †Foothills Hospital, University of Calgary, Calgary, AB, Canada Introduction: 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. Aim: 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 1 FVIII daily vs. 10 IU kg 1 EOD 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. Conclusion: 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. Keywords: daily, factor VIII, haemophilia, pharmacokinetics, prophylaxis, trough level Introduction Prophylaxis with regular infusion of clotting factor to prevent bleeds and bleed-related complications (partic- ularly deteriorating joint health status) results in increased quality of life (QoL) and is considered the standard of care for persons with severe haemophilia A (SHA) [1]. The efficacy and benefit of standard full- dose prophylaxis (factor VIII 25 IU kg 1 every other day or 39 per week) as practiced in developed countries has been demonstrated in randomized trials [2–5]. According to pharmacokinetic (PK) principles, more frequent infusions of smaller doses of FVIII can maintain a similar FVIII trough level attained by using higher doses at less frequent intervals, yet could result in lower consumption of FVIII concentrates. Two clin- ical studies have shown that daily prophylaxis results in roughly 24–30% reduction of FVIII consumption compared to standard every other day/39 per week prophylaxis [6,7]. In China, as in many resource limited countries, only low dose prophylaxis at 5–10 IU kg 1 2–3 times a week is practiced [8–12]. Although the regimen is far superior (in decreasing bleed episodes) to on demand therapy, we are looking for a strategy to improve the effectiveness of low dose prophylaxis without increasing FVIII consumption, particularly in older children and adults with higher body weight and who have good venous access. Pharmacokinetics modelling suggests improvement of trough level can be achieved by using more frequent Correspondence: Yongqiang Zhao, Department of Hematology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100730, China. Tel.: +86 10 69158271, fax: +86 10 69158271; e-mail: yongqiangzhao@hotmail.com Accepted after revision 17 December 2016 © 2017 John Wiley & Sons Ltd 1 Haemophilia (2017), 1–5 DOI: 10.1111/hae.13182