Pharmacokinetic profile of children with haemophilia A receiving low-dose FVIII prophylaxis in Indonesia: A single centre experience.

BACKGROUND: Pharmacokinetic (PK) studies of low-dose prophylaxis (LDP) of coagulation factor VIII (FVIII) in children with severe haemophilia A (SHA) are scarce. OBJECTIVE: This study aims to investigate the PK profile of children with SHA receiving LDP of FVIII. METHODS: Paediatric patients receiving FVIII infusions (10 IU/kg twice weekly) were included. PK profiles were estimated using the Web Accessible Population Pharmacokinetic Service for Haemophilia (WAPPS-Haemo). The primary outcomes were the terminal half-life (t1/2 ), concentration-time profile, and time to reach an FVIII level of < 1%. The secondary outcome was the suggested dosing interval of FVIII prophylaxis based on the individual PK profile. RESULTS: Twenty-five patients were recruited; their mean age was 12.3 ± 3.0 years. The t1/2 differed among patients receiving LDP of FVIII twice weekly, with a median of t1/2 was 14.8 h (IQR 12.6-16). The median time to reach an FVIII level of < 1% was 73.8 h (IQR 58.8-80.3). Most patients could maintain a trough level of FVIII > 1% longer than 48 h. At 72-96 h, patients needed a second dose of FVIII infusion because the FVIII level was < 1%. The suggested dosing interval of FVIII prophylaxis ranged from daily to every 96 h, depending on the individual PK profile. CONCLUSION: Our study identified inter-individual differences in the PK parameters using LDP of FVIII twice weekly. The inter-individual results in different dosing intervals advise the timing of LDP. Estimating individual PK parameters enables the identification of the optimal prophylaxis frequency to prevent bleedings.

Gut microbiome pattern in adolescents with functional gastrointestinal disease.

BACKGROUND: Functional gastrointestinal disease (FGID) has a worldwide prevalence of 10-45%, and is one of the most common causes of recurrent abdominal pain in children. FGID is characterized with abdominal discomfort and changes in bowel movement. Alteration in gut microbiota is associated with FGID, but data are limited, and there are no data from Indonesia. METHODS: A case-control study was conducted in 22 FGID children and 28 healthy subjects aged 13-18 years at the junior high school and senior high school in Central Jakarta. FGID was diagnosed using Rome IV criteria. Age, sex, and level of education were recorded. Stool samples were collected and investigated for Bifidobacterium spp. and Enterobacteriaceae. RESULTS: Most of the FGID subjects were females (17/22), with a median age of 16 years. The median values of Bifidobacterium spp. were 138.95 (range: 0.2-22,735.8) CFU/gram for the FGID subjects and 232.5 (range: 1.9-38,985.6) CFU/gram in healthy subjects, which showed no statistically significant difference (P = .49). The median values of Enterobacteriaceae were 58.9 (range: 2.5-9577.8) CFU/gram in FGID subjects and 85 (range: 12.1-3139.4) CFU/gram in healthy subjects, which showed no statistically significant difference (P = .94). Our findings indicate that the gut microbiome of adolescents with FGIDs is characterized by a huge variability in levels of Bifidobacterium spp. and Enterobacteriaceae. CONCLUSION: Because of the wide range detected in the number of Bifidobacterium spp. and Enterobacteriaceae in FGID and healthy subjects, no statistically significant difference was observed. More studies in larger groups of selected patients may be needed.