Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis.
Drug Des Devel Ther
; 10: 593-607, 2016.
Article
em En
| MEDLINE
| ID: mdl-26893546
ABSTRACT
BACKGROUND:
Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA) use in pediatric ulcerative colitis (UC).AIM:
To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC.METHODS:
Participants (5-17 years of age; 18-82 kg, stratified by weight) with UC received multi-matrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day) for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model.RESULTS:
Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg]) were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%-45%, respectively) were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were reported by ten subjects. Events were similar among different doses and age groups with no new safety signals identified.CONCLUSION:
Children and adolescents with UC receiving multimatrix mesalamine demonstrated 5-ASA and Ac-5-ASA pharmacokinetic profiles similar to historical adult data. Multimatrix mesalamine was well tolerated across all dose and age groups. ClinicalTrials.gov Identifier NCT01130844.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colite Ulcerativa
/
Anti-Inflamatórios não Esteroides
/
Mesalamina
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adolescent
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Child
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Child, preschool
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Female
/
Humans
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Male
Idioma:
En
Revista:
Drug Des Devel Ther
Ano de publicação:
2016
Tipo de documento:
Article