Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis
| Autor: | Carmen Cuffari, Alena Y Z Edwards, David M. Pierce, Stuart Hossack, Hong Wan, Patrick Martin, Heather Van Heusen, Krzysztof Fyderek, Bartosz Korczowski |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
medicine.medical_specialty Aminosalicylic acid Adolescent Pharmaceutical Science Pediatric ulcerative colitis Gastroenterology mesalamine law.invention 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Randomized controlled trial Pharmacokinetics law Internal medicine Drug Discovery Area under curve medicine Humans Child Original Research ulcerative colitis Drug Design Development and Therapy business.industry Anti-Inflammatory Agents Non-Steroidal medicine.disease Ulcerative colitis digestive system diseases Surgery Aminosalicylic Acids chemistry 030220 oncology & carcinogenesis Area Under Curve Child Preschool 030211 gastroenterology & hepatology Colitis Ulcerative Female pharmacology business |
| Zdroj: | Drug Design, Development and Therapy |
| ISSN: | 1177-8881 |
| Popis: | Carmen Cuffari,1 David Pierce,2 Bartosz Korczowski,3 Krzysztof Fyderek,4 Heather Van Heusen,5 Stuart Hossack,6 Hong Wan,5 Alena YZ Edwards,7 Patrick Martin5 1Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Shire, Basingstoke, UK; 3Medical College, University of Rzeszów, Rzeszów, Poland; 4University Children’s Hospital of Cracow, Cracow, Poland; 5Shire, Wayne, PA, USA; 6Covance Clinical Research Unit Limited, Leeds, UK; 7ICON Early Phase Services, Marlow, Buckinghamshire, UK 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 (5–17years of age; 18–82 kg, stratified by weight) with UC received multimatrix mesalamine 30, 60, or 100mg/kg/day once daily (to 4,800mg/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 [30mg/kg]; 22 [60mg/kg]; 9 [100mg/kg]) were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60mg/kg/day cohorts. For 30, 60, and 100mg/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. Keywords: ulcerative colitis, mesalamine, pharmacology |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|