Background Despite 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.

Design bioavailability microtracer population PK study

Participants patients < 6 yrs old in the pediatric ICU who received 15 mg/kg iv APAP q6h

Intervention a single microdose of ^14CAPAP (3µg/kg) given orally at the same time as a therapeutic iv dose

Data collection Blood was sampled 8 times up to 24 h post-dose

Data analysis population 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.

Results Oral 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).

Conclusion Compared 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