Pharmacokinetic Evaluation of Oral Viscous Budesonide in Paediatric Patients with Eosinophilic Oesophagitis in Repaired Oesophageal Atresia

被引:2
作者
Simeoli, Raffaele [1 ]
Lava, Sebastiano A. G. [2 ]
Di Deo, Alessandro [2 ]
Roversi, Marco [3 ]
Cairoli, Sara [1 ]
Tambucci, Renato [4 ]
Rea, Francesca [4 ]
Malamisura, Monica [4 ]
Angelino, Giulia [4 ]
Biondi, Isabella [5 ]
Simonetti, Alessandra [5 ]
De Angelis, Paola [4 ]
Dionisi Vici, Carlo [1 ]
Rossi, Paolo [5 ]
Pontrelli, Giuseppe [5 ]
Della Pasqua, Oscar [2 ]
Goffredo, Bianca Maria [1 ]
机构
[1] IRCCS, Bambino Gesu Childrens Hosp, Div Metab Dis, I-00165 Rome, Italy
[2] UCL, Clin Pharmacol & Therapeut Grp, London WC1N 3JH, England
[3] Univ Roma Tor Vergata, PhD Program Immunol Mol Med & Appl Biotechnol, I-00133 Rome, Italy
[4] IRCCS, Bambino Gesu Childrens Hosp, Digest Endoscopy Unit, I-00165 Rome, Italy
[5] IRCCS, Bambino Gesu Childrens Hosp, Ctr Excellence Dev & Implementat Med Vaccines & Me, I-00165 Rome, Italy
关键词
eosinophilic oesophagitis (EoE); oesophageal atresia (EA); pharmacokinetics; oral viscous budesonide; population pharmacokinetic modelling; systemic absorption; LC-MS/MS; CHILDREN; GUIDELINES; MANAGEMENT; SUSPENSION; DIAGNOSIS; THERAPY;
D O I
10.3390/pharmaceutics16070872
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Eosinophilic oesophagitis is a long-term complication of oesophageal atresia (EA), an uncommon condition that affects approximately 1 in 3500 infants. An exploratory, open-label phase 2 clinical trial was conducted in paediatric eosinophilic oesophagitis after oesophageal atresia (EoE-EA) to assess the safety, pharmacokinetics, and efficacy of oral viscous budesonide (OVB). In total, eight patients were enrolled in the study and assigned to a twice-daily dosing regimen of either 0.8 or 1 mg OVB, depending on age and height, administered for 12 weeks. OVB was safe and effective in the treatment of EoE-EA. The current investigation focuses on the pharmacokinetics of budesonide and the impact of an oral viscous formulation on its absorption and bioavailability. Using a non-linear mixed effects approach, two distinct absorption profiles were identified, despite marked interindividual variability in drug concentrations. Budesonide exposure was higher than previously reported in children following oral inhalation. Even though no significant effect has been observed on serum cortisol levels, future studies should consider exploring different doses, schedules, and/or treatment durations, as there may be an opportunity to reduce the risk of cortisol suppression.
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页数:12
相关论文
共 41 条
[1]   Budesonide for the treatment of ulcerative colitis [J].
Abdalla, Maisa I. ;
Herfarth, Hans .
EXPERT OPINION ON PHARMACOTHERAPY, 2016, 17 (11) :1549-1559
[2]   Oral viscous budesonide: A potential new therapy for eosinophilic esophagitis in children [J].
Aceves, Seema S. ;
Bastian, John F. ;
Newbury, Robert O. ;
Dohil, Ranjan .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2007, 102 (10) :2271-2279
[3]  
[Anonymous], 2014, R LANG ENV STAT COMP, V2014
[4]   Exposure-Response and Clinical Outcome Modeling of Inhaled Budesonide/Formoterol Combination in Asthma Patients [J].
Back, Hyun-moon ;
Lee, Jong Bong ;
Kim, Anhye ;
Park, Seon-Jong ;
Kim, Junyeong ;
Chae, Jung-woo ;
Sheen, Seung Soo ;
Kagan, Leonid ;
Park, Hae-Sim ;
Ye, Young-Min ;
Yun, Hwi-yeol .
PHARMACEUTICS, 2020, 12 (04)
[5]   Modelling and simulation as research tools in paediatric drug development [J].
Bellanti, Francesco ;
Della Pasqua, Oscar .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 2011, 67 :S75-S86
[6]   What is the right dose for children? [J].
Cella, Massimo ;
Knibbe, Catherijne ;
Danhof, Meindert ;
Della Pasqua, Oscar .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2010, 70 (04) :597-603
[7]   Pharmacokinetics and Tolerability of Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate and Glycopyrronium/Formoterol Fumarate Dihydrate Metered Dose Inhalers in Healthy Chinese Adults: A Randomized, Double-blind, Parallel-group Study [J].
Chen, Qian ;
Hu, Chaoying ;
Yu, Hui ;
Shen, Kai ;
Assam, Pryseley Nkouibert ;
Gillen, Michael ;
Liu, Yun ;
Dorinsky, Paul .
CLINICAL THERAPEUTICS, 2019, 41 (05) :897-909
[8]   Systemic side effects of inhaled corticosteroids in patients with asthma [J].
Dahl, Ronald .
RESPIRATORY MEDICINE, 2006, 100 (08) :1307-1317
[9]   Therapeutic index of inhaled corticosteroids in asthma: A dose-response comparison on airway hyperresponsiveness and adrenal axis suppression [J].
Daley-Yates, Peter T. ;
Brealey, Noushin ;
Thomas, Sebin ;
Austin, Daren ;
Shabbir, Shaila ;
Harrison, Tim ;
Singh, Dave ;
Barnes, Neil .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2021, 87 (02) :483-493
[10]   Relationship between systemic corticosteroid exposure and growth velocity: Development and validation of a pharmacokinetic/pharmacodynamic model [J].
Daley-Yates, PT ;
Richards, DH .
CLINICAL THERAPEUTICS, 2004, 26 (11) :1905-1919