{"entity": "publication", "iuid": "97c316d78160412bb2ed291ee3a6d31e", "timestamp": "2026-09-26T23:30:40.989Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/97c316d78160412bb2ed291ee3a6d31e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/97c316d78160412bb2ed291ee3a6d31e"}}, "title": "Development of a population pharmacokinetic model of prucalopride in children with functional constipation.", "authors": [{"family": "van Schaick", "given": "Erno", "initials": "E"}, {"family": "Benninga", "given": "Marc A", "initials": "MA"}, {"family": "Levine", "given": "Amy", "initials": "A"}, {"family": "Magnusson", "given": "Mats", "initials": "M"}, {"family": "Troy", "given": "Steven", "initials": "S"}], "type": "journal article", "published": "2016-08-00", "journal": {"title": "Pharmacol Res Perspect", "issn": "2052-1707", "volume": "4", "issue": "4", "pages": "e00236", "issn-l": null}, "abstract": "A recent phase 3 trial of prucalopride in children with functional constipation (SPD555-303 ClinicalTrials.gov Identifier: NCT01330381) reported negative efficacy results. Here, we developed a population pharmacokinetic (PK) model of prucalopride in children to assess prucalopride exposure in SPD555-303. An initial population PK model in children was developed based on sampled single-dose data from a phase 1 study (PRU-USA-12). This model was subsequently updated with sampled data from SPD555-303 and used to simulate plasma concentration-time profiles for children aged 6 months to 18 years who were treated once daily with prucalopride 0.02, 0.04, or 0.06 mg kg-1 (maximum dose, 2 mg). Simulated PK profiles were compared with those of adults at the recommended dose of 2 mg once daily. Data were available from 38 patients (median age, 8.5 years) in PRU-USA-12 and 137 patients (median age, 7.9 years) in SPD555-303. Mean (range) area under the plasma concentration-time curve (AUC) at steady state was 62.3 (40.5-82.7) ng mL-1 h (dose, 0.03 mg kg-1) in PRU-USA-12 and 100.3 (22.7-286.0) ng mL-1 h (dose, 0.04 mg kg-1; maximum, 2 mg) in SPD555-303. Prucalopride 0.04 mg kg-1 once daily in children produced similar maximum plasma concentrations and approximately 10% lower AUC compared with adults receiving 2 mg once daily. This population PK analysis indicates that the PK profile of prucalopride in children in SPD555-303 was similar to that observed in adults. The negative efficacy results of SPD555-303 cannot be explained by differences in prucalopride exposure between children and adults.", "doi": "10.1002/prp2.236", "pmid": "27891230", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC5114692"}, {"db": "pii", "key": "PRP2236"}, {"db": "ClinicalTrials.gov", "key": "NCT01330381"}], "notes": [], "created": "2026-09-23T13:02:37.892Z", "modified": "2026-09-23T13:02:37.939Z"}