P52 Low and erratic exposure of oral acetaminophen in critically ill children determined with a 14C microtracer study: a case for IV acetaminophen for acute pain management?

• Published in: Archives of disease in childhood 2019-06, Vol.104 (6), p.e38
• Main Authors: Kleiber, N, Calvier, E, Mooij, MG, Krekels, EHJ, Vaes, WH, Windhorst, AD, Hendrikse, H, Tibboel, D, Knibbe, CAJ, de Wildt, SN
• Format: Article
• Language: English
• Subjects: Acetaminophen; Analgesics; Bioavailability; Children; Data Analysis; Data collection; Dosage; Pain; Pain management; Patients; Pediatrics; Population studies
• ISSN: 0003-9888; 1468-2044
• DOI: 10.1136/archdischild-2019-esdppp.90

BackgroundDespite being the most commonly used analgesic and antipyretic, oral APAP bioavailability has not been determined in children. The aim of this study is to compare exposure after oral vs iv APAP using the PK data of the first pediatric oral bioavailability 14C microtracer study.MethodsDesignbioavailability microtracer population PK studyParticipantspatients < 6 yrs old in the pediatric ICU who received 15 mg/kg iv APAP q6hInterventiona single microdose of 14CAPAP (3µg/kg) given orally at the same time as a therapeutic iv doseData collectionBlood was sampled 8 times up to 24 h post-doseData analysispopulation PK analysis using NONMEM. Based on the model, exposure after oral vs iv was compared by simulating the concentration-time profiles and Css (targeted: 10 mg/L ± 20% deviation).3 doses were simulated: 15 mg/kg q6h oral and iv and 22.5 mg/kg oral q6h. 1000 simulations were performed and the percentage of patients reaching the targeted mean Css of 10 mg/L±20% were compared.ResultsOral bioavailibity was 72% (range:11–91%). After 15 mg/kg APAP, the median simulated oral Css was subtherapeutic (6.5 mg/L), but therapeutic (10 mg/L) for IV dosing (15 mg/kg). Patients were 2.5 times less likely to reach therapeutic plasma concentrations with 15 mg/kg oral vs iv APAP.With the maximal recommended oral doses of 22.5 mg/kg 6 h aimed to overcome the 72% bioavailability, median mean Css were therapeutic but overexposure and underexposure were more common than with iv (37 vs 32% Css< 8 mg/L and 30 vs 21% Css>12 mg/L).ConclusionCompared to IV, the usual (15 mg/kg) oral APAP doses result in low systemic exposure with subsequent risk of therapeutic failure. When oral doses are increased to overcome the low bioavailability, underdosing still occurs and overdosing was observed in patients with high bioavailability. IV APAP should therefore be preferred for acute pain management.Disclosure(s)Nothing to disclose